Research Topics
| Arun GhoshSummaryAffiliation: Purdue University Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Structure-based design of novel HIV-1 protease inhibitors to combat drug resistanceArun K Ghosh
Department of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 49:5252-61. 2006..35 A resolution) revealed extensive interactions in the HIV protease active site including strong hydrogen bonding interactions with the backbone. This design strategy may lead to novel inhibitors that can combat drug resistance...
Structure-based design of highly selective β-secretase inhibitors: synthesis, biological evaluation, and protein-ligand X-ray crystal structureArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States
J Med Chem 55:9195-207. 2012..A protein-ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases...- Enantioselective total synthesis of (+)-lithospermic acidArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 14:5046-9. 2012.... - Enantioselective total synthesis of pladienolide B: a potent spliceosome inhibitorArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 14:4730-3. 2012..The synthesis features an epoxide opening reaction, an asymmetric reduction of a β-keto ester, and a cross metathesis strategy for the side chain synthesis... - Structure-based design, synthesis, and biological evaluation of dihydroquinazoline-derived potent β-secretase inhibitorsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, United States
Bioorg Med Chem Lett 22:5460-5. 2012..A model of 4f was created based upon the X-ray structure of 3a-bound β-secretase. The model suggested possible interactions in the active site... - TiCl4-promoted tandem carbonyl or imine addition and Friedel-Crafts cyclization: synthesis of benzo-fused oxabicyclooctanes and nonanesArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 14:2002-5. 2012..The reaction involved a TiCl(4)-mediated tandem carbonyl or imine addition followed by a Friedel-Crafts cyclization to provide these functionalized derivatives in good to excellent yields and high diastereoselectivity... - Substituent effects on P2-cyclopentyltetrahydrofuranyl urethanes: design, synthesis, and X-ray studies of potent HIV-1 protease inhibitorsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 22:2308-11. 2012..A high-resolution X-ray crystal structure of 3c-bound HIV-1 protease revealed a number of important molecular insights into the ligand-binding site interactions... - Stereoselective synthesis of both tetrahydropyran rings of the antitumor macrolide, (-)-lasonolide AArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Org Chem 77:2559-65. 2012.... - A stereoselective synthesis of (-)-viridiofungin A utilizing a TiCl(4)-promoted asymmetric multicomponent reactionArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 14:510-2. 2012..Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia-Kocienski olefination... 
Enhancing protein backbone binding--a fruitful concept for combating drug-resistant HIVArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Angew Chem Int Ed Engl 51:1778-802. 2012....- Potent memapsin 2 (beta-secretase) inhibitors: design, synthesis, protein-ligand X-ray structure, and in vivo evaluationArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 18:1031-6. 2008..The X-ray structure of protein-ligand complex of memapsin 2 revealed critical interactions in the memapsin 2 active site... - Enantioselective total synthesis of macrolide antitumor agent (-)-lasonolide AArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 9:1437-40. 2007..The lower tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels-Alder reaction as the key step. Three stereocenters were enantioselectively installed in this single step reaction... - Capturing the essence of organic synthesis: from bioactive natural products to designed molecules in today's medicineArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
J Org Chem 75:7967-89. 2010..This paper also highlights our approach to molecular design and synthesis of conceptually novel inhibitors against target proteins involved in the pathogenesis of human diseases, including AIDS and Alzheimer's disease... - Highly diastereoselective synthesis of modified nucleosides via an asymmetric multicomponent reactionArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA
Chem Commun (Camb) 46:1218-20. 2010..We have developed a practical synthesis of unique nucleoside derivatives via TiCl(4) promoted multicomponent reaction of optically active dihydrofuran, ethyl pyruvate/glyoxylate, and a TMS protected nucleobase in a single-pot operation... - Memapsin 2 (beta-secretase) inhibitor drug, between fantasy and realityArun K Ghosh
Department of Chemistry and Medical Chemistry, Purdue University, West Lafayette, IN 47907, USA
Curr Alzheimer Res 4:418-22. 2007..This progress permits optimism that development of clinical candidates of beta-secretase inhibitor drugs is a realistic goal... - Severe acute respiratory syndrome coronavirus papain-like novel protease inhibitors: design, synthesis, protein-ligand X-ray structure and biological evaluationArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
J Med Chem 53:4968-79. 2010..A protein-ligand X-ray structure of 15 g-bound SARS-CoV PLpro and a corresponding model of 15 h docked to PLpro provide intriguing molecular insight into the ligand-binding site interactions... - Structure-based design, synthesis, and biological evaluation of peptidomimetic SARS-CoV 3CLpro inhibitorsArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 17:5876-80. 2007..Incorporation of Boc-Ser as the P(4)-ligand resulted in enhanced SARS-CoV 3CLpro inhibitory activity. Structural analysis of the inhibitor-bound X-ray structure revealed high binding affinity toward the enzyme... - Enantioselective synthesis of (-)-platensimycin oxatetracyclic core by using an intramolecular Diels-Alder reactionArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 9:4013-6. 2007..The Diels-Alder substrate was conveniently assembled in optically active form with use of (S)-carvone as the starting material... - Design, synthesis, and X-ray structure of potent memapsin 2 (beta-secretase) inhibitors with isophthalamide derivatives as the P2-P3-ligandsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 50:2399-407. 2007..A protein-ligand X-ray crystal structure of 5d-bound memapsin 2 provided vital molecular insight that can serve as an important guide to further design of novel inhibitors... - Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistanceArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Acc Chem Res 41:78-86. 2008..The concept of targeting the protein backbone in current structure-based drug design may offer a reliable strategy for combating drug resistance... - Enantioselective syntheses of the proposed structures of cytotoxic macrolides iriomoteolide-1a and -1bArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 12:3120-3. 2010..The synthesis features Julia-Kocienski olefination, Sharpless asymmetric epoxidation, Brown asymmetric crotylboration, a Sakurai reaction, an aldol reaction, and enzymatic resolution as the key steps... - Synthesis and biological evaluation of new jasplakinolide (jaspamide) analogsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 20:5104-7. 2010..All synthetic analogs were evaluated for their ability to disrupt the actin cytoskeleton. Compounds 2, 3, and 4 essentially displayed similar activity to jasplakinolide... - Enantioselective total synthesis of +-jasplakinolideArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 9:2425-7. 2007..Yamaguchi macrocyclization and removal of the protecting group provided a convenient access to (+)-jasplakinolide... - Enantioselective total synthesis of peloruside A: a potent microtubule stabilizerArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 10:1001-4. 2008.... - A symmetry-based concise formal synthesis of platencin, a novel lead against "superbugs"Arun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA
Angew Chem Int Ed Engl 48:5372-5. 2009..The synthesis utilized only one protecting group. The base-catalyzed Michael cyclization of precursor 1 afforded the key diketone 2, which was converted into the desired core structure 4 via the radical intermediate 3... - Design of HIV-1 protease inhibitors with pyrrolidinones and oxazolidinones as novel P1'-ligands to enhance backbone-binding interactions with protease: synthesis, biological evaluation, and protein-ligand X-ray studiesArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 52:3902-14. 2009.... - Asymmetric synthesis of anti-aldol segments via a nonaldol route: synthetic applications to statines and (-)-tetrahydrolipstatinArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Org Chem 74:4508-18. 2009..Oxidative cleavage of the styrene derivatives provided access to the anti-aldol segments. The utility of this methodology was demonstrated by the synthesis of statine derivatives and pancreatic lipase inhibitor, (-)-tetrahydrolipstatin... - A convergent synthesis of the proposed structure of antitumor depsipeptide stereocalpin AArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 11:1963-6. 2009..A late-stage methylation strategy led to the synthesis of the proposed structure of stereocalpin A... - Total synthesis of (-)-platensimycin, a novel antibacterial agentArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Org Chem 74:1163-70. 2009..The synthesis also featured an efficient Petasis olefination, a hydroboration sequence, a Gais's asymmetric Horner-Wadsworth-Emmons reaction, and a mercury salt catalyzed enol ether isomerization... - Design and synthesis of stereochemically defined novel spirocyclic P2-ligands for HIV-1 protease inhibitorsArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 10:5135-8. 2008..Structure-based design, synthesis of ligands, and biological evaluations of the resulting inhibitors are reported... - An asymmetric total synthesis of brevisamideArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 11:4164-7. 2009..The synthesis also features a modified Wolff-Kishner reduction, Rubottom oxidation, and Suzuki-Miyaura coupling to furnish brevisamide... - Design, synthesis, protein-ligand X-ray structure, and biological evaluation of a series of novel macrocyclic human immunodeficiency virus-1 protease inhibitors to combat drug resistanceArun K Ghosh
Department of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 52:7689-705. 2009..Protein-ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions... - L-selectride-mediated highly diastereoselective asymmetric reductive aldol reaction: access to an important subunit for bioactive moleculesArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 10:4811-4. 2008..The resulting alpha,alpha-dimethyl-beta-hydroxy ketones are inherent to a variety of biologically active natural products... - Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitorsArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 18:5684-8. 2008..9 microM. Molecular docking studies have provided possible binding modes of these inhibitors... - Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease inhibitors: design, synthesis, biological evaluation, and protein-ligand X-ray studiesArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 51:6021-33. 2008..In addition, the P2-ligand in 3d forms a unique water-mediated interaction with the NH of Gly-48... - Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylaseArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 10:3907-9. 2008.... - Synthesis and biological evaluation of novel allophenylnorstatine-based HIV-1 protease inhibitors incorporating high affinity P2-ligandsArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, United States
Bioorg Med Chem Lett 20:1241-6. 2010..Inhibitors 3b and 3c, containing conformationally constrained cyclic ethers, displayed impressive enzymatic and antiviral properties and represent promising lead compounds for further optimization... - Memapsin 2 (beta-secretase) inhibitors: drug developmentArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Curr Alzheimer Res 5:121-31. 2008..Such progress lends optimism that clinically useful memapsin 2 inhibitors will eventually be developed... - Asymmetric multicomponent reactions: diastereoselective synthesis of substituted pyrrolidines and prolinesArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Org Lett 8:4509-11. 2006..The reaction is quite efficient and constructed up to three stereogenic centers in a single operation... - A stereoselective synthesis of (+)-herboxidiene/GEX1AArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States
Org Lett 13:66-9. 2011..The synthesis of the C10-C19 segment was accomplished using Brown's crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions... - Enantioselective total synthesis of (-)-zampanolide, a potent microtubule-stabilizing agentArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 13:4108-11. 2011..The synthesis features cross-metathesis to construct the trisubstituted olefin and a ring-closing metathesis to form the macrolactone. The final N-acyl aminal formation was stereoselectively accomplished by an organocatalytic reaction... - Potent HIV-1 protease inhibitors incorporating meso-bicyclic urethanes as P2-ligands: structure-based design, synthesis, biological evaluation and protein-ligand X-ray studiesArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Org Biomol Chem 6:3703-13. 2008..A protein-ligand X-ray structure of -bound HIV-1 protease revealed a number of key hydrogen bonding interactions at the S2-subsite. We have created an active model of inhibitor based upon this X-ray structure... - Tetrahydrofuran, tetrahydropyran, triazoles and related heterocyclic derivatives as HIV protease inhibitorsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Future Med Chem 3:1181-97. 2011..This review will hopefully stimulate the widespread application of these heterocycles in the design of other therapeutic agents... - Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like proteaseArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA
J Med Chem 52:5228-40. 2009..3 microM) and the most potent SARS antiviral activity (EC(50) = 5.2 microM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS-CoV PLpro inhibitors... - Design and synthesis of peptidomimetic severe acute respiratory syndrome chymotrypsin-like protease inhibitorsArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
J Med Chem 48:6767-71. 2005..An X-ray crystal structure of our lead inhibitor (4) bound to SARS-3CLpro provided important drug-design templates for the design of small-molecule inhibitors... - Design of HIV-1 protease inhibitors with C3-substituted hexahydrocyclopentafuranyl urethanes as P2-ligands: synthesis, biological evaluation, and protein-ligand X-ray crystal structureArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Med Chem 54:5890-901. 2011..Inhibitor 26 exhibited potent activity against a panel of multidrug-resistant HIV-1 variants. A high resolution X-ray structure of 26-bound HIV-1 protease revealed important molecular insight into the ligand-binding site interactions... - Recent developments of structure based beta-secretase inhibitors for Alzheimer's diseaseAurn K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Curr Top Med Chem 5:1609-22. 2005..Here we review more recent developments in the design and testing of structure-based beta-secretase inhibitors... - Total synthesis and revision of C6 stereochemistry of (+)-amphidinolide WArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
J Org Chem 71:1085-93. 2006..Of particular note, the C6 absolute stereochemistry of amphidinolide W has now been revised through our synthesis... - Cu(II)-catalyzed olefin migration and Prins cyclization: highly diastereoselective synthesis of substituted tetrahydropyransArun K Ghosh
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, USA
Org Lett 13:4328-31. 2011..This methodology provides convenient access to a variety of functionalized tetrahydropyrans in excellent diastereoselectivities and good to excellent yields... - Bis-tetrahydrofuran: a privileged ligand for darunavir and a new generation of hiv protease inhibitors that combat drug resistanceArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
ChemMedChem 1:939-50. 2006 - Design and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P(2) ligands: structure-activity studies and biological evaluationArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, United States
J Med Chem 54:622-34. 2011..An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand... - Design, synthesis and X-ray structure of protein-ligand complexes: important insight into selectivity of memapsin 2 (beta-secretase) inhibitorsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
J Am Chem Soc 128:5310-1. 2006..A protein-ligand crystal structure revealed cooperative interactions in the S2- and S3-active sites of memapsin 2. These interactions may serve as an important guide to design selectivity over memapsin 1 and cathepsin D... - Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P2'-ligandsArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem Lett 16:1869-73. 2006..The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease... - Structure-based design: synthesis and biological evaluation of a series of novel cycloamide-derived HIV-1 protease inhibitorsArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
J Med Chem 48:3576-85. 2005..7 nM and an antiviral IC(50) value of 0.3 microM. In view of their structural simplicity and preliminary interesting results, further optimization of these inhibitors is underway... - Darunavir, a conceptually new HIV-1 protease inhibitor for the treatment of drug-resistant HIVArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Bioorg Med Chem 15:7576-80. 2007..Darunavir has recently been approved for the treatment of HIV/AIDS patients harboring multidrug-resistant HIV-1 variants that do not respond to previously existing HAART regimens... - High resolution crystal structures of HIV-1 protease with a potent non-peptide inhibitor (UIC-94017) active against multi-drug-resistant clinical strainsYunfeng Tie
Department of Chemistry, Georgia State University, Atlanta, GA 30303, USA
J Mol Biol 338:341-52. 2004..Finally, the 1.10A resolution structure of PR(V82A) with UIC-94017 showed an unusual distribution of electron density for the catalytic aspartate residues, which is discussed in relation to the reaction mechanism... - Assignment of absolute stereochemistry and total synthesis of (-)-spongidepsinArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
Org Lett 6:2055-8. 2004..has shown potent antitumor properties against a variety of NCI tumor cell lines. Our synthesis is convergent, and the absolute stereochemistry of four of the five chiral centers was assigned through synthesis... - Enantioselective synthesis of (+)-cryptophycin 52 (LY355703), a potent antimitotic antitumor agentArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
J Org Chem 68:9823-6. 2003..Both of these stereogenic centers were derived from optically active 4-phenylbutyrolactone, synthesized enantioselectively by Corey-Bakshi-Shibata reduction... - Novel cyclourethane-derived HIV protease inhibitors: a ring-closing olefin metathesis based strategyArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 60607, USA
Bioorg Med Chem Lett 12:1993-6. 2002..Ring size and substituent efffects have been investigated. Cyclourethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against HIV-1 protease... - Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase)Arun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
Bioorg Med Chem Lett 15:15-20. 2005..Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase)... - Beta-secretase as a therapeutic target for inhibitor drugsArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, USA
Curr Med Chem 9:1135-44. 2002..More recent inhibitors, having Ki values in the nanomolar range and molecular size in low 700 Da, show some promise that clinically useful inhibitors of beta-scretasse may be attainable... - Antiviral activity of UIC-PI, a novel inhibitor of the human immunodeficiency virus type 1 proteaseArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
Antiviral Res 54:29-36. 2002..In parallel studies comparing UIC-PI and saquinavir in H9/HIV-1(IIIB) cells, viral p24 levels in culture supernatants were an order of magnitude lower with UIC-PI than with saquinavir... - Stereoselective photochemical 1,3-dioxolane addition to 5-alkoxymethyl-2(5H)-furanone: synthesis of bis-tetrahydrofuranyl ligand for HIV protease inhibitor UIC-94017 (TMC-114)Arun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
J Org Chem 69:7822-9. 2004..Optically active bis-THF was converted to protease inhibitor 2 (UIC-94017)... - Chelation-controlled reduction: stereoselective formation of syn-1,3-diols and synthesis of compactin and mevinolin lactoneArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, 60607, USA
J Org Chem 67:8783-8. 2002..This methodology is utilized in a short and efficient synthesis of the delta-lactone moiety of the HMG-CoA reductase inhibitors compactin and mevinolin... - Enantioselective total synthesis of (+)-amphidinolide t1Arun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
J Am Chem Soc 125:2374-5. 2003..The bromoether derivative 24 was unraveled at the final stage of the synthesis, providing (+)-amphidinolide T1... - Stereoselective chloroacetate aldol reactions: syntheses of acetate aldol equivalents and darzens glycidic estersArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA
Org Lett 6:2725-8. 2004..Removal of chlorine provided alternative access to highly diastereoselective acetate aldol equivalents or the corresponding glycidic ester condensation products. [reaction: see text].. - Total synthesis and structural revision of (+)-amphidinolide WArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 60607, USA
J Am Chem Soc 126:3704-5. 2004..Of particular note, the C6 absolute stereochemistry of amphidinolide W (1) has now been revised through our current synthesis... - Highly diastereoselective anti-aldol reactions utilizing the titanium enolate of cis-2-arylsulfonamido-1- acenaphthenyl propionateArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
Org Lett 5:1063-6. 2003..Both enantiomers of cis-2-amino-1-acenaphthenol were synthesized employing lipase-catalyzed kinetic resolution as the key step... - Total synthesis of potent antitumor agent (-)-lasonolide A: a cycloaddition-based strategyArun K Ghosh
Departments of Chemistry and Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA
Chem Asian J 3:1811-23. 2008..The synthesis also features a Lewis acid catalyzed epoxide opening to form a substituted ether stereoselectively... - Atomic resolution crystal structures of HIV-1 protease and mutants V82A and I84V with saquinavirYunfeng Tie
Department of Chemistry, Georgia State University, Atlanta, Georgia 30303, USA
Proteins 67:232-42. 2007..This analysis will assist with development of more effective antiviral inhibitors... - Alpha-fluorovinyl Weinreb amides and alpha-fluoroenones from a common fluorinated building blockArun K Ghosh
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA
J Org Chem 74:3689-97. 2009..Application of the Weinreb amide to alpha-fluoro allyl amine synthesis is also shown... - beta-Secretase as a therapeutic target for Alzheimer's diseaseArun K Ghosh
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Neurotherapeutics 5:399-408. 2008..With this knowledge base, it seems reasonable to expect that more drug candidates will be tested in human, and then successful disease-modifying drugs may ultimately emerge from this target... - Conformations of laulimalide in DMSO-d6Pahk Thepchatri
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA
J Am Chem Soc 127:12838-46. 2005..In this way, we have identified 15 laulimalide conformations that can be classified into 5 different families: Supine, Convex, Cobra, Stretch, and Concave motifs... - High-yield synthesis of fluorinated benzothiazolyl sulfones: general synthons for fluoro-julia olefinationsArun K Ghosh
Department of Chemistry, The City College and The City University of New York, 138th Street at Convent Avenue, New York, New York 10031, USA
Org Lett 8:1553-6. 2006..The alpha-fluoro 1,3-benzothiazol-2-yl sulfones so obtained were subjected to condensations with a variety of aldehydes and ketones to afford high yields of regiospecifically fluorinated olefins... - Fluoro-Julia olefination as a mild, high-yielding route to alpha-fluoro acrylonitrilesMaria del Solar
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031 9198, USA
J Org Chem 73:8206-11. 2008..Lowering of reaction temperature increases the Z selectivity... - Fluorinated 1-phenyl-1H-tetrazol-5-yl sulfone derivatives as general reagents for fluoroalkylidene synthesisArun K Ghosh
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA
J Org Chem 74:8531-40. 2009..Dialkyl, aryl alkyl, and diaryl ketones reacted as well to give fluoro olefin products in 71-99% yields... - Direct synthesis of 8-fluoro purine nucleosides via metalation-fluorinationArun K Ghosh
Department of Chemistry, The City College and The City University of New York, 160 Convent Avenue, New York, New York 10031, USA
J Org Chem 72:8222-6. 2007..NMR data indicate a syn conformation of the 8-fluoro derivatives... - TiCl4-promoted multicomponent reaction: a new entry to functionalized alpha-amino acidsArun K Ghosh
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607, USA
Org Lett 7:7-10. 2005..Cis/trans selectivities with optically active substituted dihydrofurans have been investigated... - Altered HIV-1 Gag protein interactions with cyclophilin A (CypA) on the acquisition of H219Q and H219P substitutions in the CypA binding loopHiroyuki Gatanaga
Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, NCI, National Institutes of Health, Bethesda, MD 20892, USA
J Biol Chem 281:1241-50. 2006.... - A potent human immunodeficiency virus type 1 protease inhibitor, UIC-94003 (TMC-126), and selection of a novel (A28S) mutation in the protease active siteKazuhisa Yoshimura
Experimental Retrovirology Section, Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
J Virol 76:1349-58. 2002.... - Structural locations and functional roles of new subsites S5, S6, and S7 in memapsin 2 (beta-secretase)Robert T Turner
Protein Studies Program, Oklahoma Medical Research Foundation, Department of Biochemistry and Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA
Biochemistry 44:105-12. 2005..The crystal structure of a new inhibitor, OM03-4 (K(i) = 0.03 nM), bound to memapsin 2 revealed the interaction of a tryptophan with the S(6) subsite of the protease... - A noncovalent class of papain-like protease/deubiquitinase inhibitors blocks SARS virus replicationKiira Ratia
Center for Pharmaceutical Biotechnology and Department of Medicinal Chemistry and Pharmacognosy, University of Illinois, Chicago, IL 60607, USA
Proc Natl Acad Sci U S A 105:16119-24. 2008.... - In vivo inhibition of Abeta production by memapsin 2 (beta-secretase) inhibitorsWan-Pin Chang
Protein Studies Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
J Neurochem 89:1409-16. 2004..These observations verified that memapsin 2 is a therapeutic target for Abeta reduction and also establish that transgenic mice are suitable in vivo models for the study of memapsin 2 inhibition... - Study of memapsin 2 (beta-secretase) and strategy of inhibitor designJordan Tang
Protein Studies Program, Oklahoma Medical Research Foundation, Department of Biochemistry and Molecular Biology, Oklahoma University Medical Center, Oklahoma City, OK 73104, USA
J Mol Neurosci 20:299-304. 2003..Although development of a clinical candidate of memapsin 2 inhibitor drug remains a very challenging undertaking, the progress so far lends some optimism for future prospects... - Crystal structure of memapsin 2 (beta-secretase) in complex with an inhibitor OM00-3Lin Hong
Protein Studies Program, Oklahoma Medical Research Foundation, and Department of Biochemistry and Molecular Biology, University of Oklahoma Medical Center, Oklahoma City, Oklahoma 73104, USA
Biochemistry 41:10963-7. 2002..These new structural elements are useful for the design of new inhibitors. The structural and kinetic data indicate that the replacement of the P(2)' alanine in OM99-2 with a valine in OM00-3 stabilizes the binding of P(3)' and P(4)'... - Specificity of memapsin 1 and its implications on the design of memapsin 2 (beta-secretase) inhibitor selectivityRobert T Turner
Protein Studies Program, Oklahoma Medical Research Foundation and Department of Biochemistry and Molecular Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA
Biochemistry 41:8742-6. 2002..This difficulty was confirmed by the finding that several potent memapsin 2 inhibitors effectively inhibited memapsin 1 as well. Several possible approaches to overcome this problem are discussed... - Effectiveness of nonpeptide clinical inhibitor TMC-114 on HIV-1 protease with highly drug resistant mutations D30N, I50V, and L90MAndrey Yu Kovalevsky
Department of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, Georgia 30303, USA
J Med Chem 49:1379-87. 2006..The observed changes in PR structure and activity are discussed in relation to the potential for development of resistant mutants on exposure to TMC-114... - Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitroYasuhiro Koh
Department of Internal Medicine II, Kumamoto University School of Medicine, Kumamoto 860-8556, Japan
Antimicrob Agents Chemother 47:3123-9. 2003.... - (-)-Doliculide, a new macrocyclic depsipeptide enhancer of actin assemblyRuoli Bai
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Frederick, Maryland 21702, USA
J Biol Chem 277:32165-71. 2002..We found that the segment of (-)-doliculide that best overlapped the other molecules encompassed its phenyl and isopropyl side chains and the portion of the macrocycle between these substituents... - Structural evidence for effectiveness of darunavir and two related antiviral inhibitors against HIV-2 proteaseAndrey Y Kovalevsky
Department of Biology, Molecular Basis of Disease Program, Georgia State University, Atlanta, GA 30303, USA
J Mol Biol 384:178-92. 2008..These near-atomic-resolution crystal structures verify the inhibitor potency for PR1 and PR2 and will provide the basis for the development of antiviral inhibitors targeting PR2... - Solution kinetics measurements suggest HIV-1 protease has two binding sites for darunavir and amprenavirAndrey Y Kovalevsky
Departments of Biology and Chemistry, Molecular Basis of Disease Program, Georgia State University, Atlanta, Georgia 30303, USA
J Med Chem 51:6599-603. 2008..The inhibition model is consistent with the observed second binding site for darunavir and helps to explain its antiviral potency... - Effect of flap mutations on structure of HIV-1 protease and inhibition by saquinavir and darunavirFengling Liu
Department of Biology, Molecular Basis of Disease Program, Georgia State University, Atlanta, GA 30303, USA
J Mol Biol 381:102-15. 2008..This analysis of structural and kinetic effects of the mutants will assist in the development of more effective inhibitors for drug-resistant HIV... - Development of protease inhibitors and the fight with drug-resistant HIV-1 variantsHiroaki Mitsuya
The Experimental Retrovirology Section, HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA
Adv Pharmacol 56:169-97. 2008 - Potent new antiviral compound shows similar inhibition and structural interactions with drug resistant mutants and wild type HIV-1 proteaseYuan Fang Wang
Department of Biology, Molecular Basis of Disease, Georgia State University, Atlanta, Georgia 30303, USA
J Med Chem 50:4509-15. 2007..Therefore, inhibitor 1 is a valuable addition to the antiviral inhibitors with high potency against resistant strains of HIV... - Potent inhibition of HIV-1 replication by novel non-peptidyl small molecule inhibitors of protease dimerizationYasuhiro Koh
Department of Hematology, Kumamoto University Graduate School of Medical and Pharmaceutical Sciences, 1 1 1 Honjo, Kumamoto 860 8556, Japan
J Biol Chem 282:28709-20. 2007..Such a dual inhibition mechanism should lead to highly potent inhibition of HIV-1... - A novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI), GRL-98065, is potent against multiple-PI-resistant human immunodeficiency virus in vitroMasayuki Amano
Departments of Infectious Diseases and Hematology, Kumamoto University School of Medicine, 1 1 1 Honjo, Kumamoto 860 8556, Japan
Antimicrob Agents Chemother 51:2143-55. 2007.... - Ultra-high resolution crystal structure of HIV-1 protease mutant reveals two binding sites for clinical inhibitor TMC114Andrey Y Kovalevsky
Department of Biology, Molecular Basis of Disease, GA State University, Atlanta, GA 30303, USA
J Mol Biol 363:161-73. 2006..The existence of the second binding site and two diastereomers suggest a mechanism for the high effectiveness of TMC114 on drug-resistant HIV and the potential design of new inhibitors... - Laulimalide and paclitaxel: a comparison of their effects on tubulin assembly and their synergistic action when present simultaneouslyEric J Gapud
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnostics, National Cancer Institute at Frederick, Frederick, MD 21702, USA
Mol Pharmacol 66:113-21. 2004..When radiolabeled GTP is present in a reaction mixture with either laulimalide or paclitaxel, nucleotide hydrolysis occurs with incorporation of radiolabeled GDP into polymer... - The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activityDonald E Pryor
Screening Technologies Branch, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA
Biochemistry 41:9109-15. 2002..Further exploration of the role of the epoxide in the interaction of laulimalide with tubulin is therefore justified... - Synergistic effects of peloruside A and laulimalide with taxoid site drugs, but not with each other, on tubulin assemblyErnest Hamel
Toxicology and Pharmacology Branch, Developmental Threapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute at Frederick, MD 21702, USA
Mol Pharmacol 70:1555-64. 2006....
Research Grants
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun Ghosh; Fiscal Year: 2005..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train students in the laboratory. ..
- DEVELOPMENT OF LIGAND ASSISTED ASYMMETRIC SYNTHESESArun Ghosh; Fiscal Year: 2001..Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory. ..
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun Ghosh; Fiscal Year: 2001....
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun Ghosh; Fiscal Year: 2009..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun K Ghosh; Fiscal Year: 2010..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..
- DESIGN AND SYNTHESIS OF NONPEPTIDE PROTEASE INHIBITORSArun Ghosh; Fiscal Year: 2009..This research integrates organic synthesis, protein-ligand x-ray crystallography, molecular modeling and in-depth virus and cell-biological studies to design the next generation of HIV-1 protease inhibitors. ..