Ahmed Kamal

..These PBD conjugates have exhibited good DNA binding affinity, and a representative compound shows promising in vitro anticancer activity...

..Despite encouraging observed results for their response to tumors in clinical studies, full characterization of their toxicity is further required for their clinical usage as safe drugs for the treatment of cancer...

..The utility of naphthalimide derivatives as novel pharmaceutical and photochemical agents can be further enhanced by introducing polar side chains and fusing functionalized heterocyclic rings with naphthalimide cores...

..Further, Hoechst 33258 staining and DNA fragmentation assay also suggests that 17g induces cell death by apoptosis...

..Docking experiments have shown that the active molecules interact and bind well in the ATP binding pocket of ERK protein...

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..Overall, the current study demonstrates that the synthesis of chalcone-amidobenzothiazole conjugates as promising anticancer agents with potent G2/M arrest and apoptotic-inducing activities via targeting tubulin...

..The cytotoxicity of 4i correlated with induction of apoptosis, caspases activation and DNA damage and thus indicating the apoptotic pathway of anticancer effect of these compounds...

..Compounds 3t and 3ad are the most promising candidates amongst the series and has the potential to be taken up for further detailed studies either alone or in combination with the existing therapies...

..Moreover activation of caspase-3, p21, p16, NF-kB and down regulation of Bcl-2 protein suggests that this compound (11e) has apoptotic cell death inducing ability, apart from acting as a topo-IIα inhibitor...

..We believe that this review gives a better understanding and scope for future drug design and development of benzothiazole-based compounds to implicate their use in cancer chemotherapy...

..The metabolites from Pseudomonas sp. strain ICTB-745 have interesting potential for use as a biopesticide in pest control programs...

..One of the representative compound 3e could be considered as the potential lead for its development as a new anticancer agent...

..Further, Hoechst 33258 staining and DNA fragmentation assay also suggested that 17a and 17f induced cell death by apoptosis...

..This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis...

..Hence these PBD conjugates with 6a being the most potent one could be be taken up for preclinical studies either alone or in combination with existing therapies...

..Future epidemiological research into the efficacy of omega-3 PUFA in cardiovascular disease should consider the influence of ethnicity...

..Further, the compound 17d was evaluated for in vivo efficacy studies in human colon cancer HT29 xenograft mice...

..These compounds showed the characteristic features of apoptosis like enhancement in the levels of p53, release of cytochrome c, and cleavage of PARP...

..2, 1.2, 3.6 and 3.6 microM, respectively, against DU-145 cell line. Interestingly, some of the compounds are selectively potent in prostate cancer (DU-145) with IC(50) values of 1.2-19.6 microM...

..Further, to understand structural requirements for exploring the structure activity relationship of BTDs, cytotoxicity and in vivo study of recently reported potent molecule 4 (MIC = 1 microg/mL) is also discussed...

..Interestingly, compounds 5b and 6b have been identified as a new class of inhibitors of tubulin polymerization and their action has been rationalized by the cell cycle arrest in G0 and G2/M phase...

..These promising compounds showed the characteristic features of apoptosis like enhancement in the levels of p53 and activation of caspase-3...

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..Our findings suggested the phenanthrylphenol-PBD conjugate 4c, which is a cyclin D1 inhibitor could be considered as a promising lead compound against breast cancer for further investigation...

..Therefore, the data generated suggests that these PBD conjugates activate p53 and inhibit NF-kappaB and thereby these compounds could be promising anticancer agents with better therapeutic potential for the suppression of tumours...

..We have also attempted to highlight the efforts that are being made in the development of new molecules based on thiolactomycin as lead compound, including studies from this laboratory...

..Some representative C2-fluoro substituted dimers (8a and 14a) have also exhibited significant anticancer activity in the 60 cancer cell line assay of the National Cancer Institute (NCI)...

..5 mol%) as a novel catalyst. Further, some of the synthesized compounds were evaluated for their efficacy as antibacterial and antifungal activities. Most of the compounds have shown moderate to good inhibitory activity...

..Their DNA thermal denaturation studies have also been carried out, and one of the compounds 5c elevates the DNA helix melting temperature of the CT-DNA by 2.6 degrees C after incubation for 36 h...

..Some detailed biological assays relating to the cell cycle aspects associated to Bax and caspases have been examined with a view to understand the mechanism of action of these conjugates...

..One of these chalcone derivatives, 3 d, is potentially well suited for detailed biological studies, either alone or in combination with existing therapies...

..The ease of synthesis and interesting biological activities make the present series of polyaromatic-podophyllotoxin congeners as a promising new structure for the development of new anticancer agents based on podophyllotoxin scaffold...

..Molecular modeling studies provided a molecular basis for the favorable binding of compounds 3 a, 3 e, and 3 h to the colchicine binding pocket of tubulin...

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..One conjugate in particular is the most promising candidate of the series, with the potential to be selected for further studies, either alone or in combination with existing anticancer therapies...

..These findings suggest that one of the compound 4d among this series is most effective and has potential for detailed investigations...

..abstract:..

..Further, compounds 6g and 6i are also evaluated for their DNA topoisomerase-II (topo-II) inhibition activity and they exhibited significant inhibition of topo-II catalytic activity comparable to etoposide...

..Further studies showed that cancer cell growth inhibition by compounds 22 and 23 could be in part due to the inhibition of tubulin polymerization, with the IC50 values of 4.70 and 5.25 µM, respectively...

..5 μM (IC50) concentration of compound 7l and induced apoptosis. This was confirmed by Annexin V-FITC as well as DNA fragmentation analysis and interestingly this compound (7l) did not affect the normal cells...

..Further, the DNA binding ability by thermal denaturation studies and antimicrobial activities of these compounds are also discussed...

..Flow cytometric analysis showed that these compounds (11a, 11k and 11p) arrested the cell cycle in the G2/M phase of cell cycle leading to caspase-3 dependent apoptotic cell death...

..ruber AKSH-84, which can be used in green biosynthesis of acrylic acid for biotechnological processes. The nitrilase produced by the isolate was purified and characterized...

..Finally, these studies suggest that compounds 7c and 9a may serve as promising lead scaffolds for further generation of new as anti-TB agents...

..Further some detailed biological assays relating to the cell cycle aspects and tubulin depolymerization activity have been examined with a view to understand the mechanism of action of this conjugate...

..Some of the representative compounds have been evaluated for their cytotoxicity against selected human cancer cell lines and DNA topoisomerase-II inhibition activity...

..Among all these conjugates, one of the compound 5c could be considered as the most effective compound particularly against MCF-7 breast cancer cell line...

..Pyrrolobenzodiazepine hybrids linked to acridone/acridine ring systems at C8-position have been designed and prepared that exhibit significant DNA-binding affinity, and a representative compound shows promising in vitro anticancer activity...

..Further, benzothiadiazinone, thioxoquinazolinone, cinnoline and indazole are also examined in this review...

..Further, the most relevant biological properties of these heterocycles have also been incorporated...

..One of the compound (4b), elevates the DNA helix melting temperature of the CT-DNA by 2.0 degrees C after incubation for 36 h at 37 degrees C...

..However, the in vivo testing in a mouse model of tuberculosis infection did not show significant anti-tubercular activity, probably because of its poor bioavailability...

..Interestingly, these dimers 6a-d are significantly more cytotoxic than 4 in a number of human cancer cell lines, in particular, compound 6c is highly potent for almost all the nine human cancer cell lines...

..Some of these compounds have exhibited promising in vitro anticancer and topo-II inhibition activity...

..Some of the compounds have exhibited potential activity against Mycobacterium tuberculosis...

..Some of these new compounds inhibited the growth of Mycobacterium tuberculosis ATCC 27294, Mycobacterium avium ATCC 49601, Mycobacterium intracellulare ATCC 13950 and some clinical isolates...

..An efficient and facile chemoenzymatic synthesis of levamisole by employing lipase-mediated resolution of 3-hydroxy-3-phenylpropanenitrile followed by its conversion to beta-amino alcohol as the key intermediate is described...

..0 degrees C) when compared to naturally occurring DC-81, 1 (DeltaTm=0.7 degrees C). The imine-amine PBD dimers exhibit promising in vitro antitumor activity in a number of human cancer cell lines...

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..New pyrrolobenzodiazepine-anthraquinone hybrids have been designed and synthesized, found to effectively bind to DNA and also exhibit cytotoxicity against many cancer cell lines..

..These PBD conjugates have exhibited remarkable DNA-binding affinity, and a representative compound shows promising in vitro anticancer activity...

..The synthesis of novel A-C8/C-C2-exo unsaturated alkoxyamido-linked pyrrolo[2,1-c][1,4]benzodiazepine dimers is reported and these dimers show significant DNA binding affinity and they also exhibit moderate anticancer activity...

..QSAR models developed in these studies will be helpful in the future to design novel potent bispodophyllotoxin analogues by minor structural modifications...

..Most of these compounds showed better inhibitory activity in comparison to the standard drugs...

..8 degrees C after incubation of 36 h at 37 degrees C...

..These pyrrolobenzodiazepine conjugates have exhibited remarkable DNA-binding affinity and improved solubility in water, a representative compound 7d showing promising in vitro cytotoxicity...

..Interestingly, some of these molecules have shown enhanced DNA-binding affinity and promising anticancer activity on a large number of human cancer cell lines...

..Some of these conjugates show significant DNA-binding affinity and, a representative compound 4c shows promising in vitro cytotoxicity against a number of human cancer cell lines...

..Enhanced water solubility and improved stability are the other important outcomes upon modifying these molecules as their prodrugs...

..Some of these molecules have shown significant anticancer activity in a number of cancer cell lines...

..These new conjugates exhibit very high DNA binding affinity and cytotoxic activity against a number of cell lines...

..Their DNA thermal denaturation studies have been carried out and one of the compounds (4b) elevates the DNA helix melting temperature of the CT-DNA by 6.7 degrees C after incubation for 36 h...

..Surprisingly, the increased concentration of the same compound to 30 microM caused accumulation of cells in G0/G1 phase of the cell cycle...

..One of the compounds 2f has shown good in vitro antimycobacterial activity. All the synthesized compounds have shown moderate to good antibacterial activity...

..The final crude products were purified from excess amines by solid-supported liquid-liquid extraction (SLE)...

..Another important property of these molecules is their enhanced water solubility and stability, which are essential for a molecule to be an effective drug...

..coli as well as Bacillus subtilis. Moreover, other compounds also showed potent inhibitory activity in comparison to the standard drugs...

..Some of these new hybrid compounds showed higher cytotoxic activity than the existing natural and synthetic pyrrolo[2,1-c][1,4]benzodiazepines...

..C2-Fluoro substituted pyrrolobenzodiazepines (PBDs) have been synthesized that exhibit potential anticancer activity in a number of human tumour cell lines. These C2-fluoro substituted PBDs also exhibit significant DNA-binding ability...

..These molecules have exhibited promising DNA-binding affinity and anticancer activity in selected human cancer cell lines...

..A series of C2-exo-fluorounsaturated pyrrolobenzodiazepines (PBDs) have been synthesized. These C2-exo-fluorounsaturated PBD dimers have exhibited remarkable DNA-binding affinity...

..In this review both the synthetic strategies and the structure-activity relationships, particularly the DNA binding and cytotoxicity studies of PBDs have been discussed...

..These have been prepared by linking the amines at C-8 position with propane spacer to improve solubility in water, and their in vitro cytotoxicity studies have been carried out...

..The energy of interaction in all of the complexes studied is correlated to the DeltaT(m) values. Furthermore, this dimer 5c has significant cytotoxicity in a number of human cancer cell lines...

..The synthesis of new A-C8/C-C2 alkoxyamido-linked pyrrolo[2,1-c][1,4]-benzodiazepine dimers have been described in this report. These dimers exhibit significant DNA-binding ability with moderate anticancer activity...

..Further, from a generated library of 210 compounds, 142 compounds have been selected and evaluated for in vitro activity against Mycobacterium tuberculosis, and some of these compounds have exhibited promising activity...

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..These 4beta-amido and 4beta-sulphonamido derivatives of podophyllotoxin have been evaluated for their cytotoxicity against six human cancer cell lines. Some of these analogues have shown promising anticancer activity...

..The mechanistic aspects have been investigated and the intermediates associated with this selective transformation have been intercepted and characterized by online monitoring of the reaction by ESI-MS...

..Synthesis of C2 and C2-C8 linked pyrrolobenzodiazepine-naphthalimide hybrids have been prepared that exhibit significant DNA-binding affinity and cytotoxicity...

..These have been prepared by linking the methanesulphonate at C-8 position with alkanol spacer and their in vitro cytotoxicity have been described...

..Chrysene-linked pyrrolobenzodiazepine hybrids have been prepared that possess cytotoxicity in some cancer cell lines. They also exhibit promising DNA-binding affinity and this is supported by molecular modeling studies...

..These hybrids also exhibit much enhanced DNA-binding ability in comparison to the parent pyrrolobenzodiazepine ring system (DC-81)...

..Immobilized Pseudomonas cepacia lipase offered high degree of enantioselectivity with spontaneity...

..One of the synthesized compounds (5b) exhibited significant inhibitory activity against most of the cell lines and has been further evaluated for the five-dose screening...

..This methodology has been extended for the preparation of new nicotinamido-pyrrolobenzodiazepine hybrids linked through piperazino-alkane-oxy spacers that exhibit good DNA binding affinity...