Synthesis, and biological screening of chloropyrazine conjugated benzothiazepine derivatives as potential antimicrobial, antitubercular and cytotoxic agents

• Main Authors: Shaik, Afzal B, Bhandare, Richie R, Nissankararao, Srinath, Lokesh, Bontha Venkata Subrahmanya, Shahanaaz, Shaik, Rahman, M.Mukhlesur
• Format: Article
• Published: Elsevier 2021
• Subjects: QD Chemistry
• Online Access: http://eprints.um.edu.my/35974/; https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098452918&doi=10.1016%2fj.arabjc.2020.102915&partnerID=40&md5=13d61cb3c7f3973944420707daae2ea6
• Institution: Universiti Malaya

A series of twenty new chloropyrazine conjugated benzothiazepines (22–41) have been synthesized with 58–95 yields. The compounds were characterized by using different spectroscopic techniques including FT-IR, 1H NMR, 13C NMR spectroscopy and mass spectrometry. The synthesized compounds (22–41) and their precursor chalcones (2–21) were evaluated for antitubercular and cytotoxic activities. Additionally, compounds 22–41 were also tested for antimicrobial activity. Among the chalcone series (2–21), compounds 7 and 14 showed significant antitubercular activities (MICs 25.51 and 23.89 µM, respectively), whereas among benzothiazepines (22–41), compounds 27 and 34 displayed significant antimicrobial (MICs 38.02 µM, 19.01 µM) and antitubercular (MIC 18.10 µM) activities. Compounds 7 and 41 displayed cytotoxic activities with IC50 of 46.03 ± 1 and 35.10 ± 2 µM respectively. All the compounds were evaluated for cytotoxic activity on normal human liver cell lines (L02) and found to be relatively less selective towards this cell line. The most active compounds identified through this study could be considered as potential leads for the development of drugs with possible antimicrobial, antitubercular, and cytotoxic activities. © 2020 The Author(s)