Synthesis, cytotoxicity, in-vitro antibacterial screening and in-silico study of novel thieno[2,3-b]pyridines as potential pim-1 inhibitors

Abstract

A novel series of thieno[2,3-b]pyridines was prepared via an one-step protocol in excellent yields. The protocol involved the reaction of pyridine-2(1H)-thiones with the appropriate halogen containing reagents in ethanolic sodium ethoxide solution under stirring at 80 °C for 2 h. The new thienopyridines were screened against different bacterial and fungal strains. Thieno[2,3-b]pyridine-2-carboxylate 9a showed the most effective antibacterial activities against each of Staphylococcus aureus and Escherichia coli with MIC/MBC values of 9.9/19.8 and 19.8/39.5 µM, respectively, when compared with Ciprofloxacin. 9a was the most effective compound against MRSA with inhibition zone of 16.2 ± 0.6 mm, when compared with Gentamicin. Moreover, 9a exhibited the best cytotoxic activity against each of HEPG2 and MCF-7 cell lines with IC₅₀ values of 25.7 and 30.53 µM, respectively, when compared with Doxorubicin. The in-silico study was performed to predict the capability of new thienopyridines as potential inhibitors of pim-1 kinase.

Graphical Abstract

Keywords:

• In-silico study
• in-vitro antimicrobial activity
• pim-1 inhibitors
• pyridine-2(1H)-thione
• thieno[23-b]pyridine