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 one-pot 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 μg/ml for C. albicans and C. glabrata whereas C. tropicalis showed a slightly higher MIC of 440 μg/ml. Compound 9 gave an MIC of 465 μg/ml for C. albicans, 470 µg/ml for C. glabrata while 485 μg/ml for C. tropicalis. The antibacterial activity against gram-positive (E. coli) and gram-negative (S. aureus) was investigated. Compound 6 showed MIC 12 μg/ml for E. coli and 12 μg/ml for S. aureus. While compound 9 showed MIC 6 μg/ml and 12 μg/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.