Design, Synthesis, Neuroprotective and Antibacterial Activities of 1,2,4‐Triazolo[3,4‐b]1,3,4‐thiadiazole Linked Thieno[2,3‐d]pyrimidine Derivatives and In Silico Docking Studies

Abstract

Abstract In pursuit of neuroprotective and antimicrobial agents, a series of 1,2,4‐triazolo[3,4‐b]1,3,4‐thiadiazole incorporated thieno[2,3‐d]pyrimidine derivatives 10 a‐l has been designed, synthesized. The final target compounds were screened for neuroprotective, neurotoxic and antibacterial activities. The compounds derived from 4‐methylphenyl ( 10 a ) and 4‐nitrophenyl ( 10 c ) have showed good neuroprotective activity against H 2 O 2 induced PC12 cell death at respective EC 50 values of 10.44, 14.12 μg/mL. However 10 b and 10 k showed superior neurotoxic effects than rest of the compounds with respective CC 50 values of 100.16, 120 μg/mL. Potent antibacterial activity was shown by 10 f (R=‐Me, R 2 =‐OMe), 10 h (R=‐Me, R 2 =‐Cl) against the four bacterial pathogens such as S.aureus , B.subtilis, E.coli and P.aeruginosa at low minimum inhibitory concentration (MIC) range. Further, in silico docking studies were performed for all the synthesized compounds with C(30) carotenoid dehydrosqualene synthase, Gyrase A and LpxC bacterial proteins. Interestingly, 10 f, 10 h showed good binding affinities with target proteins and these results are in good compliance with the in vitro activity profile data.