Synthesis, characterization, biological screenings and molecular docking study of Organotin(IV) derivatives of 2,4-dichlorophenoxyacetic acid

Abstract

New tri- and diorganotin (IV) derivatives of 2,4-dichlorophenoxyacetic acid with general formula: R3SnL and R2SnL2: {Me3SnL (1), Bu3SnL (2), Me2SnL2 (3), Bu2SnL2 (4) and Oct2SnL2 (5), L = 2,4-dichlorophenoxyacetate} have been synthesized and characterized in solid state by elemental and FT-IR analysis, whereas in solution state by 1H and 13C NMR spectroscopy. Compound 1 was also characterized by single crystal X-ray crystallography. The FT-IR data of compounds 1–5 confirm the bidentate binding mode of ligand with penta and hexa-coordinated arrangements around the Sn(IV) centre in solid state. The value of CSnC angle for complexes 1 and 3 calculated from NMR (1H and 13C) data using Lockart's equation were 114.7° and 114.9°, respectively which falls in the range of 5-coordinated geometry. The DNA binding of synthesized compounds were studied via UV–Vis spectroscopy and viscometry resulting in an intercalative mode of interaction. Molecular docking analysis of the studied compounds also supports the results of the UV–vis and viscometry. Moreover, interaction of the synthesized compounds with a cationic surfactant i.e., cetyltrimethyl ammonium bromide (CTAB) has been studied by conductometric method. Enzyme inhibition activity against α-amylase and α-glucosidase was carried out and compound 3 was found to possess maximum inhibition (88.1% and 91.3%, respectively). The theoretical study also enforce the experimental data for enzyme inhibition of the compound 3 (docking score = −12.4096) by forming seven hydrogen bonds and two pi-H linkages with the Glu 276, Ala 278, Phe 300, Arg 312, Tyr 313, Asp 349, Asn 412, Phe 430 and Arg 439 residues of the binding pocket of the α-glucosidase. The potency of the compound 3 might be due to the presence of the strong electron withdrawing chloro group. IC50 value of the brine shrimp activity revealed that triorganotin (IV) derivatives (1 and 2) were more toxic than their diorganotin (IV) analogues. Moreover, compound 2 has the MIC values of 12.5 μg/mL and 6.25 μg/mL against S. Aureus and M. Leuteus bacterial strains, respectively.