Novel 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives: synthesis, in vitro antitumor activity and computational studies

作者：Maddila Suresh; Naicker Kovashnee; Momin Mehbub I K; Rana Surjyakanta; Gorle Sridevi; Maddila Suryanarayana; Yalagala Kotaiah; Singh Moganavelli; Koorb****ly Neil A; Jonnalagadda Sreekantha B

来源：Medicinal Chemistry Research, 2016, 25(2): 283-291.

DOI：10.1007/s00044-015-1482-x

• Synthesis
• Tetrazoles
• Antitumor activity
• MEK-1 inhibition

This work describes the two-step synthesis of new series of 2-(1-(substitutedbenzyl)-1H-tetrazol-5-yl)-3-phenylacrylonitrile derivatives (6a-k) starting from substituted benzyl halides (5a-k) and 3-phenyl-2-(1H-tetrazol-5-yl)acrylonitrile (4). Initially, compound 4 was synthesized using benzaldehyde, malononitrile and sodium azide. All the synthesized compounds were obtained in good yields and were characterized using H-1 NMR, C-13 NMR, FTIR and HRMS spectral data. The new compounds (6a-k) were evaluated for their potential in vitro antitumor activity against four human cancer cell lines (MCF-7, CaCO2, HeLa and SkBr(3)) by MTT assay. The most potent compounds 6b, 6h and 6j show good activity (IC50 values) relative to 5-fluorouracil, with potential to be antitumor agents. Compounds 6a, 6c, 6g, 6f and 6k showed moderate activity. The best performing three compounds (6b, 6h and 6j) were evaluated for in silico analysis on the PharmMapper web server, and the human mitogen-activated protein kinase 1 (MEK-1) enzyme was recognized as the main target protein. MEK-1 inhibition by these compounds was further confirmed by the docking study to corroborate the target.

• 出版日期2016-2