Crystal structure, spectroscopic analysis, electronic properties and molecular docking study of costunolide for inhibitor capacity against Onchocerca volvulus main protease

Abstract

Costunolide, a naturally occurring sesquiterpene lactone, was investigated experimentally and theoretically to determine the structural, electronic, spectroscopic, and chemical reactivity properties. As deduced from a single crystal X-ray diffraction (XRD) analysis, the absolute configurations of the two chiral centres were assigned as (6R,7S). Vibrational frequencies (IR, UV and NMR), electronic properties (HOMO and LUMO), and the molecular structure of costunolide were investigated by DFT calculations using Gaussian 09 molecular package at the B3LYP/6-311++G(d,p) level of theory. NMR chemical shifts were calculated from the magnetic shielding tensors obtained through the gauge-independent atomic orbital (GIAO) method, while the UV-vis spectrum was simulated by time dependent-DFT (TD-DFT) calculations. All calculations showed correlations to experimental data. The 6-311+G(2d,p) basis set was additionally used for better correlation in NMR studies. The first order hyperpolarizability value indicated that costunolide has nonlinear optical (NLO) properties. Costunolide stability arising from hyperconjugative interactions and charge delocalisation was analysed using natural bond orbital (NBO). Thermodynamic parameters also correlated in the temperature range 100–700 K. The molecular docking results showed that costunolide binds strongly to the Onchocerca volvulus main protease with a relative binding affinity of –5.94 kcal mol–1 and an inhibition constant of 44.61 µM.