Synthesis, anti-angiogenic and DNA cleavage studies of novel N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)piperidine-4-carboxamide derivatives

Springer Science and Business Media LLC - Tập 11 - Trang 1-11 - 2017
Vinaya Kambappa1,2, G. K. Chandrashekara1, N. D. Rekha3, Prasanna D. Shivaramu4, Komaraiah Palle2
1Department of Chemistry, Government First Grade College, Kadur, India
2Department of Oncological Sciences, Mitchell Cancer Institute, USA Mitchell Cancer Institute, Mobile, USA
3Department of Studies in Biotechnology, JSS College of Arts, Commerce & Science, Mysore, India
4Department of Nanotechnology, Visvesvaraya Technological University, Center for Postgraduate Studies, Ckikkaballapur, India

Tóm tắt

A series of novel N-(4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)piperidine-4-carboxamide derivatives 10(a–f), 12(a–c) and 14(a–c) were synthesized and characterized by FTIR, 1H-NMR, mass spectral and elemental analysis. The efficacy of these derivatives to inhibit in vivo angiogenesis was evaluated using chick chorioallantoic membrane (CAM) model and their DNA cleavage abilities were evaluated after incubating with calf thymus DNA followed by gel electrophoresis. These novel piperidine analogues efficiently blocked the formation of blood vessels in vivo in CAM model and exhibited differential migration and band intensities in DNA binding/cleavage assays. Among the tested compounds 10a, 10b, 10c, 12b, 14b and 14c showed significant anti-angiogenic and DNA cleavage activities compared to their respective controls and the other derivatives used in this study. These observations suggest that the presence of electron donating and withdrawing groups at positions 2, 3 and 4 of the phenyl ring of the side chain may determine their potency and as anticancer agents by exerting both anti-angiogenic and cytotoxic effects .

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