Assessment of iridoids and their similar structures as antineoplastic drugs by in silico approach.

Iridoids commonly found in plants as secondary metabolites have been reported to possess significant biological activities such as anticancer, antioxidant, hypoglycemic, antimicrobial etc. The strong interactions of iridoids with cyclic-dependent kinase 8 (CDK8) protein could show inhibitory effects that could modulate tumour growth. From the molecular docking calculations, some iridoids interacted effectively with the target CDK8 protein (PDB ID: 5ICP) with better binding affinities of -9.1, -9.0, -9.0, -8.9 kcal/mol, than that observed for the native ligand with -8.7 kcal/mol and for the reference compound gemcitabine with -6.9 kcal/mol. The GI50 values (<5 µM) obtained from graph-based signatures showed activity in breast, colon, leukaemia, and renal cancer cell lines. The IC50 predictions as CDK2 inhibitors were greater than 10 µM with type I non-allosteric binding mode. The stability analysis of protein-ligand complex from 125 ns long molecular dynamics simulations showed moderately smooth trajectories and RSMD value around 5 Å for the docked ligands. The binding free energy changes up to -47.65 ± 5.97 kcal/mol from MMGBSA method and -30.33 ± 5.40 kcal/mol from MMPBSA method hinted at the spontaneous nature of the complex formation. Furthermore, geometrical evaluators like RMSF, Rg, SASA, and hydrogen bond count also corroborated with the structural stability of the complexes and the capacity of hit molecules to inhibit the target, indicating its therapeutic potential against cancer. The toxicity and drug-likeness from ADMET predictions suggested experimental verification and that the proposed candidates could be employed for further trials in the development of safer and more effective anticancer drugs.Communicated by Ramaswamy H. Sarma.

Triazole based Schiff bases and their oxovanadium(IV) complexes: Synthesis, characterization, antibacterial assay, and computational assessments.

The synthesis and characterization of two new Schiff base ligands containing 1,2,4-triazole moieties and their oxovanadium(IV) complexes have been reported. The ligands and their complexes were studied by ultraviolet-visible (UV-Vis), Fourier transform infrared (FTIR), proton nuclear magnetic resonance (1H NMR), electron paramagnetic resonance (EPR), X-ray diffraction (XRD), conductivity measurement, cyclic voltammetry (CV), and elemental analyses. The molar conductance of oxovanadium(IV) complexes were found to be relatively low, depicting their non-electrolytic nature. The XRD patterns reveal the size of particles to be 47.53 nm and 26.28 nm for the two complexes in the monoclinic crystal system. The molecular structures, geometrical parameters, chemical reactivity, stability, and frontier molecular orbital pictures were determined by density functional theory (DFT) calculations. The theoretical vibrational frequencies and EPR g-factors (1.98) were found to correlate well with the experimental values. A distorted square pyramidal geometry with C2 symmetry of the complexes has been proposed from experimental and theoretical results in a synergistic manner. The antimicrobial sensitivity of the ligands and their metal complexes assayed in vitro against four bacterial pathogens viz. Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella Typhi showed that the oxovanadium(IV) complexes are slightly stronger antibacterial agents than their corresponding Schiff base precursors. The binding affinities obtained from the molecular docking calculations with the receptor proteins of bacterial strains (2EUG, 3UWZ, 4GVF, and 4JVD) showed that the Schiff bases and their oxovanadium(IV) complexes have considerable capacity inferring activeness for effective inhibition. The molecular dynamics simulation of a protein-ligand (4JVD-HL2) complex with the best binding affinity of -12.8 kcal/mol for 100 ns showed acceptable stability of the docked pose and binding free energy of -15.17 ± 2.29 kcal/mol from molecular mechanics-generalized Born surface area (MM-GBSA) calculations indicated spontaneity of the reaction. The outcome of the research shows the complementary role of computational methods in material characterization and provides an interesting avenue to pursue for exploring new triazole based Schiff's bases and its vanadium compounds for better properties.