Regioselective synthesis and preliminary cytotoxic activity properties of tetrazole appendage N-substituted piperazine derivatives

Kommula Dileep, Mohana Rao Katiki, Busam Ramalingeswara Rao, V. P. S. Vishnu Vardhan, Ramakrishna Sistla, Jagadeesh Babu Nanubolu, Madugula Sree Rama Murty

Medicinal Chemistry & Pharmacology Division , Discovery Laboratory, CSIR–Indian Institute of Chemical Technology, Hyderabad, India

Centre for X-Ray Crystallography , CSIR–Indian Institute of Chemical Technology, Hyderabad, India.

Abstract: A series of 1-(4-substituted)-4-(3-((1-(substituted)-1H-tetrazol-5-yl)thio)propyl)piperazine derivatives were ( 6a-t) synthesized by KF-Al2O3 mediated S-alkylation of 5-thio-substituted tetrazole with 1-(3-chloropropyl)-4-(4-substituted)piperazine. The structures of the newly synthesized compounds were characterized by NMR and MS spectral data. Further, the regioselective formation of C-S bond was unambiguously confirmed by single crystal X- ray diffraction. All the synthesized compounds were screened for their in vitro cytotoxic activities against two cancer cell lines: DU-145 (prostate cancer) and HeLa (cervical cancer). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin, and their IC 50 values were determined. Among the compounds tested, 6f, 6j, 6m, 6n, 6o, 6q, 6r and 6t showed considerable potent activity, while the compound 6p exhibited significant potent activity against DU-145 and HeLa cancer cell lines compare to standard Doxorubicin.

Keywords : Tetrazole; cytotoxic activity; piperazine . © 2017 ACG Publications. All rights reserved.