One-pot multicomponent synthesis and antimicrobial evaluation of steroidal benzo[4,5]imidazo[1,2-a]pyrimidines with hemolytic assay and molecular docking studies

A novel class of steroidal benzo[4,5]imidazo[1,2-a]pyrimidine derivatives was successfully synthesized via onepot three component synthesis of pregnenolone, malononitrile, and 2-aminobenzimidazole using triethylamine as a catalyst. All the synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR and mass spectra. The synthesized compounds were tested for antifungal and antibacterial activities, and strong antifungal and antibacterial activities were observed in compounds 6 and 9. The antifungal activity of the synthesized compounds was screened against C. albicans, C. glabrata, and C. tropicalis. Compound 6 exhibited a MIC of 420 mu g/ml for C. albicans and C. glabrata whereas C. tropicalis showed a slightly higher MIC of 440 mu g/ml. Compound 9 gave an MIC of 465 mu g/ml for C. albicans, 470 mu g/ml for C. glabrata while 485 mu g/ml for C. tropicalis. The antibacterial activity against gram-positive (E. coli) and gram-negative (S. aureus) was investigated. Compound 6 showed MIC 12 mu g/ml for E. coli and 12 mu g/ml for S. aureus. While compound 9 showed MIC 6 mu g/ml and 12 mu g/ml for E. coli and S. aureus respectively. The hemolytic assay was also performed on human red blood cells. Compounds 6, 8 and 9 were found to be least toxic to human RBCs, showing 7.32 %, 7.27 % and 7.68 % cell inhibition at MIC, respectively. Furthermore, molecular docking analysis was carried out.