Affiliation: Birla Institute of Technology and Science
- Nkizinkiko Y, Suneel Kumar B, Jeankumar V, Haikarainen T, Koivunen J, Madhuri C, et al. Discovery of potent and selective nonplanar tankyrase inhibiting nicotinamide mimics. Bioorg Med Chem. 2015;23:4139-49 pubmed publisher..They also inhibited Wnt/Î²-catenin pathway in a cell-based reporter assay demonstrating the potential usefulness of the identified new scaffolds for further development. ..
- Alluri K, Reshma R, Suraparaju R, Gottapu S, Sriram D. Synthesis and evaluation of 4',5'-dihydrospiro[piperidine-4,7'-thieno[2,3-c]pyran] analogues against both active and dormant Mycobacterium tuberculosis. Bioorg Med Chem. 2018;26:1462-1469 pubmed publisher..04?±?0.32?µM. This compound is a good candidate for drug development owing to potential against both active and dormant stages of MTB. ..
- Chandran M, Renuka J, Sridevi J, Pedgaonkar G, Asmitha V, Yogeeswari P, et al. Benzothiazinone-piperazine derivatives as efficient Mycobacterium tuberculosis DNA gyrase inhibitors. Int J Mycobacteriol. 2015;4:104-15 pubmed publisher..Furthermore, it is believed that this class of compounds has the potential to be further developed as an anti-TB drug candidate. ..
- Malapati P, Krishna V, Nallangi R, Srilakshmi R, Sriram D. Identification and development of benzoxazole derivatives as novel bacterial glutamate racemase inhibitors. Eur J Med Chem. 2018;145:23-34 pubmed publisher..It also exhibited significant activity in Mtb nutrient starvation model (2.5) and Mtb biofilm model (2.4) and inÂ vivo M. marinum infected Zebra fish model studies (3.6) reduction at logarithmic scale. ..
- Samala G, Kakan S, Nallangi R, Devi P, Sridevi J, Saxena S, et al. Investigating structure-activity relationship and mechanism of action of antitubercular 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione [CD59]. Int J Mycobacteriol. 2014;3:117-26 pubmed publisher..Further screening of these molecules was required in the in vitro dormant MTB models. ..
- Saxena S, Renuka J, Yogeeswari P, Sriram D. Discovery of Novel Mycobacterial DNA Gyrase B Inhibitors: In Silico and In Vitro Biological Evaluation. Mol Inform. 2014;33:597-609 pubmed publisher..16±0.25?µM, and M. smegmatics GyrB IC50 of 1.5±0.12?µM and hence could be further developed as novel inhibitor for mycobacterial GyrB. ..
- Jeankumar V, Reshma R, Vats R, Janupally R, Saxena S, Yogeeswari P, et al. Engineering another class of anti-tubercular lead: Hit to lead optimization of an intriguing class of gyrase ATPase inhibitors. Eur J Med Chem. 2016;122:216-231 pubmed publisher..Early pharmacokinetic evaluation of the optimized analogue was encouraging and provides interesting potential for further optimization. ..
- Samala G, Devi P, Saxena S, Meda N, Yogeeswari P, Sriram D. Design, synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors. Bioorg Med Chem. 2016;24:1298-307 pubmed publisher..53Â±0.13 Î¼M, MIC of 3.53 Î¼M, 2.1 log reduction against nutrient starved MTB, with 33% cytotoxicity at 50 Î¼M. It also showed 1.5 log reduction of M. marinum load in Zebra fish at 10mg/kg. ..
- Medapi B, Suryadevara P, Renuka J, Sridevi J, Yogeeswari P, Sriram D. 4-Aminoquinoline derivatives as novel Mycobacterium tuberculosis GyrB inhibitors: Structural optimization, synthesis and biological evaluation. Eur J Med Chem. 2015;103:1-16 pubmed publisher..3 Â°C in melting temperature (Tm) when compared to the native protein thereby reacertaining the stabilization effect of the compound over protein. ..
- Devi P, Sridevi J, Kakan S, Saxena S, Jeankumar V, Soni V, et al. Discovery of novel lysine É›-aminotransferase inhibitors: An intriguing potential target for latent tuberculosis. Tuberculosis (Edinb). 2015;95:786-794 pubmed publisher..8 log reduction against nutrient starved MTB, with little cytotoxicity at a higher concentration (>50Â Î¼M). It also exhibited 1.5 log reduction of M.Â marinum load in inÂ vivo zebra fish model at 10Â mg/kg. ..
- Saxena S, Devi P, Soni V, Yogeeswari P, Sriram D. Identification of novel inhibitors against Mycobacterium tuberculosis L-alanine dehydrogenase (MTB-AlaDH) through structure-based virtual screening. J Mol Graph Model. 2014;47:37-43 pubmed publisher..Thus, we report the identification of best five hits based on structure-based design and their in vitro enzymatic inhibition studies revealed IC?? values in the range of 35-80 ?M. ..
- Reshma R, Saxena S, Bobesh K, Jeankumar V, Gunda S, Yogeeswari P, et al. Design and development of new class of Mycobacterium tuberculosisl-alanine dehydrogenase inhibitors. Bioorg Med Chem. 2016;24:4499-4508 pubmed publisher..83±0.12?M, 2.0log reduction in nutrient starved dormant MTB model and MIC of 11.81?M in actively replicative MTB. ..
- Jeankumar V, Reshma R, Janupally R, Saxena S, Sridevi J, Medapi B, et al. Enabling the (3 + 2) cycloaddition reaction in assembling newer anti-tubercular lead acting through the inhibition of the gyrase ATPase domain: lead optimization and structure activity profiling. Org Biomol Chem. 2015;13:2423-31 pubmed publisher
- Jeankumar V, Kotagiri S, Janupally R, Suryadevara P, Sridevi J, Medishetti R, et al. Exploring the gyrase ATPase domain for tailoring newer anti-tubercular drugs: hit to lead optimization of a novel class of thiazole inhibitors. Bioorg Med Chem. 2015;23:588-601 pubmed publisher..Furthermore the compounds displayed good safety profile in their subsequent cytotoxicity and hERG toxicity evaluations, to be worked out from a pharmaceutical point of view as potential anti-tubercular agents. ..
- Medapi B, Meda N, Kulkarni P, Yogeeswari P, Sriram D. Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors. Bioorg Med Chem. 2016;24:877-85 pubmed publisher..21Â±0.51Î¼M; MTB MIC of 6.59Î¼M and no zHERG cardiotoxicity at 30Î¼M and 11.78% inhibition at 50Î¼M against mouse macrophage cell line RAW 264.7. ..
- Jeankumar V, Saxena S, Vats R, Reshma R, Janupally R, Kulkarni P, et al. Structure-Guided Discovery of Antitubercular Agents That Target the Gyrase ATPase Domain. ChemMedChem. 2016;11:539-48 pubmed publisher..tuberculosis. Structural handles were also identified that will provide a suitable foundation for further optimization of these potent analogues. ..
- Bobesh K, Renuka J, Srilakshmi R, Yellanki S, Kulkarni P, Yogeeswari P, et al. Replacement of cardiotoxic aminopiperidine linker with piperazine moiety reduces cardiotoxicity? Mycobacterium tuberculosis novel bacterial topoisomerase inhibitors. Bioorg Med Chem. 2016;24:42-52 pubmed publisher..29Â±0.22Î¼M, with a good MTB MIC of 3.45Î¼M. These kind of compounds retains good potency and showed reduced cardiotoxicity compared to aminopiperidines. ..
- Medapi B, Renuka J, Saxena S, Sridevi J, Medishetti R, Kulkarni P, et al. Design and synthesis of novel quinoline-aminopiperidine hybrid analogues as Mycobacterium tuberculosis DNA gyraseB inhibitors. Bioorg Med Chem. 2015;23:2062-78 pubmed publisher..62 Â± 0.16 Î¼M. Further, compound 45 also exhibited commendable MTB MIC, safe eukaryotic cytotoxic profile with no signs of cardiotoxicity in zebrafish ether-a-go-go-related gene (zERG). ..
- Abdu Allah H, Youssif B, Abdelrahman M, Abdel Hamid M, Reshma R, Yogeeswari P, et al. Synthesis and anti-mycobacterial activity of 4-(4-phenyl-1H-1,2,3-triazol-1-yl)salicylhydrazones: revitalizing an old drug. Arch Pharm Res. 2017;40:168-179 pubmed publisher..Accordingly, we introduce compound 20 as a valuable lead for further development. A 3D-QSAR study was also conducted to help in explaining the observed activity and to serve as a tool for further development. ..
- Reshma R, Jeankumar V, Kapoor N, Saxena S, Bobesh K, Vachaspathy A, et al. Mycobacterium tuberculosis lysine-?-aminotransferase a potential target in dormancy: Benzothiazole based inhibitors. Bioorg Med Chem. 2017;25:2761-2771 pubmed publisher..38±1.21µM). Compound 22 exhibits bactericidal action against nutrient starved Mycobacterium tuberculosis (MTB). It also exhibits significant activity in nutrient starvation model (2.9log folds) and biofilm model (2.3log folds). ..
- Malapati P, Siva Krishna V, Nallangi R, Meda N, Reshma Srilakshmi R, Sriram D. Lead identification and optimization of bacterial glutamate racemase inhibitors. Bioorg Med Chem. 2018;26:177-190 pubmed publisher..32?±?0.43??M. It also showed significant activity (represented in log reduction) in nutrient starved dormant M. tuberculosis model (2.1), M. tuberculosis biofilm assay (2.0) and in vivo M. marinum infected zebrafish model (3.5). ..
- Jeankumar V, Renuka J, Pulla V, Soni V, Sridevi J, Suryadevara P, et al. Development of novel N-linked aminopiperidine-based mycobacterial DNA gyrase B inhibitors: scaffold hopping from known antibacterial leads. Int J Antimicrob Agents. 2014;43:269-78 pubmed publisher..Furthermore, the compounds did not show any signs of cardiotoxicity in zebrafish ether-à-go-go-related gene (zERG), and hence constitute a major breakthrough among the otherwise cardiotoxic N-linked aminopiperidine analogues. ..
- Samala G, Brindha Devi P, Saxena S, Gunda S, Yogeeswari P, Sriram D. Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis. Bioorg Med Chem. 2016;24:5556-5564 pubmed publisher..0 log reduction) at same dose level. Compound 5c also showed activity against MTB alanine dehydrogenase enzyme with IC50 of 1.82±0.42?M and showed 25% cytotoxicity against RAW 264.7 cell line at 50?g/mL. ..
- Reshma R, Yogeeswari P, Sriram D. Design and development of novel inhibitors for the treatment of latent tuberculosis. Int J Mycobacteriol. 2016;5 Suppl 1:S121-S122 pubmed publisher..This molecule requires further pharmacokinetic and dynamic screening for development as new drug candidate. ..