Bioactive heteroleptic Bismuth(V) carboxylates: Synthetic Stratagem, characterization and binding pattern validation

Abstract A series of heteroleptic triorganobismuth(V) carboxylates (1–8) of general formula Ar3Bi(COOR)2; where Ar = C6H5 (1–4), p-CH3C6H4 (5–8) and R = C10H7 (1, 5), 2-CH3C6H4 (2, 6), 3, 4- (OCH2CH3)C6H3 (3, 7), 2-ClC6H4 (4, 8); were synthesized by a stoichiometric reaction between the precursor, Ar3BiBr2, and the respective carboxylic acidusing triethylamine as a base in dry toluene. They were characterized by FT-IR, NMR spectroscopy and X-ray diffraction technique to get unequivocal evidence for their structural motifs. The single crystal XRD data for (2 & 5) revealed the existence of five coordinated bismuth centre having distorted trigonal bipyramidal molecular geometry, whereas (6) described weakly hexacoordinated bismuth including a unique anisobidentate interaction of one carboxyl group with the resultant distorted octahedral molecular geometry. The molecular docking studies demonstrate that compounds (1, 2 and 7) give significant GOLD fitness scores of 60.09, 62.65 and 56.30 against EGFR tyrosine kinase, human pancreatic alpha amylase and H. pylori urease respectively. The synthesized compounds were also preliminary screened for their antimicrobial, α-amylase inhibition and protein kinase inhibition activities to determine their biological efficacy. The antibacterial activity profile for (2) looks good with MIC value 6.25 μg/mL against E. coli whereas, (1, 2 and 5) show significant antifungal activity against A. flavus having MIC value of 6.25 μg/mL and the values are comparable to the reference drug(s). Compound (6) displays significant % alpha amylase inhibition of 34.80, whereas (2) exhibit 30 mm bald inhibition zone for protein kinase inhibition study, thus, proving their worth as moderate enzyme inhibitors. The molecular docking studies for (1–8) demonstrate strong interactions between the receptor and the molecule and a firm protein-ligand complex formation described their effective role in enzymes’ inhibition. The bioactivity data obtained from both in silico analysis and in vitro studies are quite promising ones and the synthesized compounds may find a leading role in future drug discovery programs.