X-Ray Crystal Structure, Spectroscopic Analysis, Computational Quantum Chemical and Molecular Docking Studies of a Naturally Occurring Sesquiterpene Lactone: Costunolide for Inhibitor Capacity Against the Main Protease of the Parasitic Worm Onchocerca Volvulus

Abstract

A naturally occurring sesquiterpene lactone, named costunolide, has been investigated experimentally and theoretically to obtain its thorough structural, electronic, spectroscopic, and biochemical activity. As deduced from a single crystal X-ray diffraction (XRD) analysis, the absolute configurations of the two chiral centres were reliably assigned as (6R,7S) with a Flack parameter of 0.01(6). Vibrational frequencies (FT-IR, UV and NMR), electronic properties (HOMO and LUMO energies), and molecular structure of costunolide have been investigated by density functional theory (DFT) method at the B3LYP/6-311++G(d,p) level of theory, in the Gaussian 09 molecular package. NMR chemical shifts were calculated from the magnetic shielding tensors obtained through the gauge-independent atomic orbital (GIAO) method by also applying the same basis set, while the ultraviolet-visible (UV-vis) data were simulated by time dependent-DFT (TD-DFT) calculations. The calculated and experimental vibrational spectra showed high correlation coefficients. The electric dipole moment, polarizability and the first order hyperpolarizability values of costunolide have been calculated at the same level of theory and basis set. The calculation results showed that the molecule has nonlinear optical (NLO) behaviour with non-zero values. Stability of the molecule arising from hyperconjugative interactions and charge delocalisation has been analysed using natural bond orbital (NBO) analysis. In addition, the changes of thermodynamic properties have been obtained in the range of 100–700 K. The molecular docking results showed that costunolide strongly binds to Onchocerca volvulus main protease by relative binding affinity of –5.94 kcal/mol and inhibition constant of 44.61 µM.

Note:
Funding Declaration: Authors are grateful to the German Academic Exchange Service (DAAD) for the financial support to the Yaoundé-Bielefeld Graduate School of Natural Products with Antiparasite and Antibacterial activities (YaBiNaPA), project N° 57316173. We also thank The World Academy of Science (TWAS) (grant N° FR3240303654), and the Alexander von Humboldt Foundation for equipment subsidies to our laboratory at the Higher Teacher Training College, University of Yaoundé I. We are also grateful to the University of KwaZulu-Natal, South Africa for the workstation used for the docking studies.

Conflict of Interests: The authors declare no conflict of interest.

Keywords: Costunolide, Single crystal XRD, NBO analysis, NLO properties, Vibrational frequencies, Molecular Docking