Synthesis, antimicrobial evaluation, α-amylase inhibitory ability and molecular docking studies of 3-alkyl-1-(4-(aryl/heteroaryl)thiazol-2-yl)indeno[1,2-c]pyrazol-4(1H)-ones

Abstract

A series of thiazole tethered indenopyrazoles has been synthesized and assayed for their antimicrobial and α-amylase inhibitory activities. Ciprofloxacin and Fluconazole were used as standard drugs for antibacterial and antifungal evaluation, respectively while Acarbose was used as standard reference for α-amylase inhibitory activity. The antimicrobial activity evaluation results revealed that derivative 3d showed highest potency against two Gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus), two Gram-negative bacterial strains (Escherichia coli and Pseudomonas aeruginosa) with MIC values of 0.0541 µmol/mL, 0.0270 µmol/mL, 0.0270 µmol/mL, 0.0270 µmol/mL, respectively and two fungal strains (Candida albians and Aspergillus niger) with MIC values of 0.0067 µmol/mL and 0.0270 µmol/mL, respectively in comparison to the standard drugs Ciprofloxacin (MIC = 0.0094 µmol/mL) and Fluconazole (MIC = 0.0408 µmol/mL). Interestingly, all the compounds of the series except 3e exhibited better inhibitory activity against C. albicans with MIC value ranging from 0.0067 to 0.0297 µmol/mL than the standard drug Fluconazole. However, derivatives 3j with IC50 value of 0.79 µM and 3k with IC50 value of 0.46 µM were recognized as good α-amylase inhibitors as compared to the reference drug Acarbose (IC50 = 0.11 µM). Further, the docking studies were performed to support the results of biological activities.