- Design and synthesis of novel heterofused pyrimidine analogues as effective antimicrobial agents
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A total of 66 novel heterofused pyrimidine analogues (pyrazolo[3,4-d]pyrimidine (7-43) and pyrido[2,3-d]pyrimidine (51a-l & 52a-h)) were synthesized by employing suitable methods. The desired structures of all the synthesized compounds were confirmed based on FT-IR, 1H NMR, 13C NMR and HRMS experimental data. Further, 19F NMR and 1H-15N HMBC of the representative compound were presented. All the final compounds were screened for their in vitro antitubercular (Mycobacterium tuberculosis; H37 Rv), antibacterial (S. aureus, B. subtilis, E. coli and P. aeruginosa) and antifungal (C. neoformans, C. albicans and A. niger) activities. Compounds 51d, 51j, 51k, 51l, and 51g displayed good antibacterial and antifungal activity (MIC = 12.5 μg/ml) against bacterial and fungal strains, while moderate inhibition (MIC = 59 μM) was observed for 51l against H37 Rv strain.
- Chandrasekaran, Balakumar,Cherukupalli, Srinivasulu,Karunanidhi, Sivanandhan,Kajee, Afsana,Aleti, Rajeshwar Reddy,Sayyad, Nisar,Kushwaha, Babita,Merugu, Srinivas Reddy,Mlisana, Koleka P.,Karpoormath, Rajshekhar
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p. 246 - 255
(2019/02/15)
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- Synthesis, anticancer evaluation, and molecular docking studies of some novel 4,6-disubstituted pyrazolo[3,4-d]pyrimidines as cyclin-dependent kinase 2 (CDK2) inhibitors
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A novel series of 4,6-disubstituted pyrazolo[3,4-d]pyrimidines (7–43) bearing various anilines at C-4 position and thiophenethyl or thiopentane moieties at C-6 position have been designed and synthesized by molecular hybridization approach. All the synthesized compounds were evaluated for in vitro CDK2/cyclin E and Abl kinase inhibitory activity as well as anti-proliferative activity against K-562 (chronic myelogeneous leukemia), and MCF-7 (breast adenocarcinoma) cell lines. The structure–activity relationship (SAR) studies revealed that compounds with thiophenethyl group at C-6 with mono-substituted anilines at C-4 exhibited better CDK2 inhibitory activity compared to alkyl group (thiopentane) at C-6 and di-substituted anilines at C-4 of the scaffold. In particular, compounds having 2-chloro, 3-nitro and 4-methylthio aniline groups at C-4 displayed significant enzymatic inhibitory activity against CDK2 with single digit micromolar IC50 values. The in silico molecular docking studies suggested possible binding orientation and the binding energies were in agreement with the observed SAR as well as experimental results. In addition, some of the synthesized compounds showed anti-proliferative effects against K-562 and MCF-7 cancer cell lines with IC50 values in a micromolar range. Thus, the synthesized compounds could be considered as new anticancer hits for further lead optimization.
- Cherukupalli, Srinivasulu,Chandrasekaran, Balakumar,Kry?tof, Vladimír,Aleti, Rajeshwar Reddy,Sayyad, Nisar,Merugu, Srinivas Reddy,Kushwaha, Narva Deshwar,Karpoormath, Rajshekhar
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- Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies
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A series of new pyrazolo[3,4-d]pyrimidine possessing 4-(1H-benzimidazol-2-yl)-phenylamine moiety at C4 position and primary as well as secondary amines at C6 position has been designed and synthesized. Their antitumor activities were evaluated against a panel of 60 human cancer cell lines at National Cancer Institute (NCI). Six compounds displayed potent and broad spectrum anticancer activities at 10?μM. Compounds 8, 12, 14 and 17 proved to be the most active and efficacious candidate in this series, with mean GI50values of 1.30?μM, 1.43?μM, 2.38?μM and 2.18?μM, respectively against several cancer cell lines. Further biological evaluation of these compounds suggested that these compounds induce apoptosis and inhibit human topoisomerase (Topo) IIα as a possible intracellular target. UV-visible and fluorescence studies of these compounds revealed strong interaction with ct-DNA and bovine serum albumin (BSA).
- Singla, Prinka,Luxami, Vijay,Singh, Raja,Tandon, Vibha,Paul, Kamaldeep
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- Oxadiazole derivatives as a novel class of antimitotic agents: Synthesis, inhibition of tubulin polymerization, and activity in tumor cell lines
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Oxadiazole derivatives were synthesized and evaluated for their ability to inhibit tubulin polymerization and to cause mitotic arrest in tumor cells. The most potent compounds inhibited tubulin polymerization at concentrations below 1 μM. Lead analogs caused mitotic arrest of A431 human epidermoid cells and cells derived from multi-drug resistant tumors (10, EC50 = 7.8 nM). Competition for the colchicine binding site and pharmacokinetic properties of selected potent compounds were also investigated and are reported herein, along with structure-activity relationships for this novel series of antimitotic agents.
- Ouyang, Xiaohu,Piatnitski, Evgueni L.,Pattaropong, Vatee,Chen, Xiaoling,He, Hai-Ying,Kiselyov, Alexander S.,Velankar, Avdhoot,Kawakami, Joel,Labelle, Marc,Smith II, Leon,Lohman, Julia,Lee, Sui Ping,Malikzay, Asra,Fleming, James,Gerlak, Jason,Wang, Ying,Rosler, Robin L.,Zhou, Kai,Mitelman, Stan,Camara, Margarita,Surguladze, David,Doody, Jacqueline F.,Tuma, M. Carolina
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p. 1191 - 1196
(2007/10/03)
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