Zero Hunger (SDG 2), Good Health & Well-being (SDG 3)
Quantitative structure binding energy study and molecular docking of xerantholide analogues Moola M. Nyambe 1* , Edet F. Archibong 2 , Kazhila C. Chinsembu 3 1 Department of Physics, Chemistry and Material Science, Faculty of Agriculture, Engineering and Natural Sciences, University of Namibia (UNAM), 2 Department of Pharmaceutical Sciences, School of Pharmacy, Faculty of Health Sciences and Veterinary Medicine, UNAM. 3 Higher Education Authority, Lusaka, Zambia. E-mail: nyambem@unam.na Theoretically, xerantholide has been shown to bind Neisseria gonorrhoeae carbonic anhydrase (NgCA) with affinity comparable to that of standard carbonic anhydrase inhibitor acetazolamide. This study assessed the binding potential of 83 sesquiterpene lactone (SL) analogues of xerantholide to NgCA. Molecular docking was used to screen the SLs for NgCA inhibition potential. Further, the active site of NgCA was modelled with zinc-tris imidazole, ([ZnIm 3 ] 2+ ) and the binding energy of the 83 SL-[ZnIm 3 ] 2+ complexes computed at the B3LYP/6-311++G(d,p) level. The compounds docked with binding score ranging from -5.3 and -7.4 kcal/mol and the binding involved hydrogen bonding, van der Waals, and hydrophobic interactions. The binding energy of complexes ranged from -16.5 to -43.1 kcal/mol. The results showed that the lactone ring is essential for strong binding which is enhanced by substituent groups such as epoxides, ketones and esters. Using QSPR study, models were developed to find the relationship between the binding energies of the SLs-Zn[Im 3 ] 2+ complexes and the molecular descriptors derived for the SLs. The generated models showed that the binding energy of the SLs-Zn[Im 3 ] 2+ complex was highly influenced by minimum electrostatic potential (MinElPot), hydrogen bond donor, HOMO, LUMO, logS and P-Area. Key words: Molecular docking, xerantholide, sesquiterpenes lactone, Neisseria gonorrhoeae. References 1. Nyambe, M.M, Archibong, E.F, Chinsembu, K.C. (2022). A DFT and molecular docking study of xerantholide and its interaction with Neisseria gonorrhoeae carbonic anhydrase. Journal of Computational Biology and Chemistry. 101, 107779.
P27
© The Author(s), 2025
Made with FlippingBook Learn more on our blog