From synthesis to bioactivity: Characterization, crystallography, antimalarial and antimicrobial activities of hydrazone-derived organotin(IV) complexes

Abstract

In the pursuit of therapeutic agents against malarial and microbial infections, a series of pentacoordinated organotin(IV) complexes [R2SnL1-4] were synthesized through the reaction of 2-acetyl/2-benzoyl-1H-indene-1,3(2H)-dione and 4-methyl/4-methoxybenzohydrazides with R2SnCl2 (R = Me, Et, n-Bu, Ph). The compounds underwent comprehensive characterization through a diverse range of spectral and physicochemical methods, encompassing (1H, 13C, 119Sn) NMR, FT-IR, HRMS, UV–vis, TGA and molar conductance. To further validate the structural details of the synthesized complexes, SC-XRD analysis was carried out on representative complex 13 [Me2SnL3], which revealed a monoclinic crystal system with space group P21/c (No. 14) and exhibiting a distorted square pyramidal geometry surrounding the tin metal center, wherein two enolic oxygen atoms occupy axial positions and equatorial positions are occupied by azomethine nitrogen atom along with two methyl carbon atoms. The antimalarial efficacy of the compounds was screened against P. falciparum, the most virulent species responsible for widespread malaria-related morbidity and mortality. The organotin(IV) complexes demonstrated superior inhibition, particularly phenyltin(IV) complexes exhibited highest inhibition, with some complexes achieving IC50 values comparable to standard drug. Notably, compounds 16 [Ph2SnL3], 19 [Bu2SnL4] and 20 [Ph2SnL4] emerged as the most active with IC50 values ranging from 0.33 to 0.36 μg/mL. Furthermore, varying levels of effectiveness were observed against all microbial pathogens. The compounds exhibited noteworthy activity, with complexes 16 and 20 exhibiting the most potent antimicrobial properties against all the tested strains with MIC values lying from 0.0046 to 0.0048 µmol/mL. Results of molecular docking showed that the most potent compound (20) interacted with several residues within the active center and exhibited a binding energy of −7.5, −10.3, and −9.6 kcal/mol for C. albicans, S. aureus and P. falciparum, respectively. Further, the ADMET score demonstrated acceptable pharmacokinetics and drug-like effects of the compounds. The study introduces the idea of the synthesized compounds as potential drug candidates.