Tridentate xanthene-based hydrazone ligands and their mononuclear transition metal complexes: synthesis, anti-malarial, antimicrobial and molecular docking studies

Abstract

In the search of potential multi-target medicinal agents, new NOO-tridentate hydrazone ligands (H2L1–H2L4) (1–4) and their transition metal(II) complexes (5–20) were synthesized from salicylaldehyde derivatives and xanthene-9-carboxylic acid hydrazide. The synthesized compounds were well characterized by different techniques, such as FT-IR, (1H, 13C) NMR, mass spectrometry, UV–Vis, ESR, TG–DTA, powder-XRD, SEM-EDAX and molar conductivity measurements. The spectral techniques confirmed the tridentate nature of hydrazones and coordination of ligands with metal ion via Nazomethine, Ophenolic and Oenolic (NOO) which suggested octahedral stereochemistry of the complexes. The complexes were obtained in good yield, non-electrolytic in nature and stable up to 150 °C. The compounds (1–20) were screened for in vitro anti-malarial activity against Plasmodium falciparum 3D7 strain and the Co(II) complex (5) (IC50 = 0.94 ± 0.03 nM) exhibited comparable potency to quinine (IC50 = 0.826 ± 0.02 nM), whereas, Cu(II) complex (19) (IC50 = 0.65 ± 0.05 nM) have excellent potency to control malarial infection. Furthermore, the in vitro antimicrobial activity against six strains revealed that the compounds 5 and 19 demonstrated greater efficacy to inhibit the growth of microbial strains among the tested compounds (1–20). The most potent anti-malarial compounds (1, 5, 19) were examined by molecular docking study against Dihydroorotate dehydrogenase protein receptor (PDB ID: 1TV5) to accomplish the acquired biological results through binding energy and interaction mode.