Synthesis, DFT study, molecular docking and larvicidal activity of Chitin inhibitor alanine derived compounds

Abstract

In order to obtain an effective larvicidal against A. aegypti the vectors for Dengue, Zika and Chikungunya virus, Sodium 2-{(E)-[(2-hydroxy-3-methoxyphenyl) methylidene] amino} propanoate (NaLH) ligand and its Cu(II) complexes derived from alanine amino acid with and without coligand (C1 &C2) have been synthesized. All three molecules were characterized by physicochemical techniques including FTIR, UV–Vis, proton NMR and Mass spectrum. The geometry optimization and frontier orbitals HOMO, LUMO and band gaps were calculated by using B3LYP functional and SVP basis sets for all three compounds (NaLH, complex C1 and C2). The values of HOMO/LUMO energies observed were −4.2/−1.7 eV for ligand, −5.2–3.5 eV for C1 and −5.0/−3.7 eV for C2 and corresponding values of energy gaps were 2.5 eV, 1.7 eV and 1.3 eV for NaLH, C1 and C2 respectively which increases in the following order NaLH > C1 > C2. Complex1 has been arranged in slightly distorted octahedral geometry while complex2 acquired a square pyramidal geometry. Molecular docking study of the reported larvicidal against insect acetylcholistenerase (PDB id: 6ARY) and Chitin acetylase (PDB id 5ZNT) revealed significant free energy of binding in the active site of target molecules with binding energy of −6.14 & −10.20Kcal/mol and −6.79 & −11.75Kcal/mol for C1 &C2 respectively. In addition, Larvicidal activity of complex 2 was observed with 100% mortality rate in just 2 hrs time using 1.0% concentration of larvicide. The LC50 value is 0.0015 µg/mL while LC90 value is 0.0018 µg/mL for C2. The complexes were observed to be lethal against Chitinous body layer of larvae of Aedes aegypti, the vectors for Dengue, Zika and Chikungunya virus.