Books (DBMB)

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    Anti-gonococcal activity of extracts from selected Namibian medicinal plants and computational studies of xerantholide, a neisseria gonorrhoeae inhibitor
    (University of Namibia, 2023) Nyambe, Moola M.
    Neisseria gonorrhoeae, the causative agent of a sexually transmitted infection, gonorrhea, has developed resistance to all available antibiotics. It is found in humans only and if left untreated can lead to serious complications such as infertility and disseminated gonococcal infections. The search for new effective, affordable, and readily accessible drugs for the treatment of gonorrhea thus continues. Plants have been a good source of structurally diverse lead compounds from which drugs have been developed. Various communities in Namibia commonly use plants in traditional health care for the treatment of sexually transmitted infections (STIs). However, these plants have not yet been evaluated for their anti-gonococcal activity and human safety. Therefore, this study aimed to isolate compounds from plants that are traditionally used to treat gonorrhea, ascertain their anti-gonococcal activity, and elucidate the structures of these compounds in an effort towards searching for selective anti-gonococcal agents. Another aim was to employ computational approaches, including density functional theory (DFT), molecular docking, prediction of activity spectra for substances (PASS) and Quantitative Structure-Property Relationship (QSPR), to model the interaction of xerantholide and its analogues with the active site of Neisseria gonorrhoeae carbonic anhydrase (NgCA) and to investigate the geometry, electronic structure, and biological activity spectra. Agar well diffusion and broth microdilution methods were used to determine the minimum inhibitory concentration (MIC) of extracts. Isolation and characterization of compounds were done using thin layer chromatography (TLC), column chromatography, x-ray diffraction and nuclear magnetic resonance (NMR). Crude extracts from six plants were ii confirmed to have anti-gonococcal activity (MIC 2.5-5.0 mg/mL). Xerantholide, with an MIC50 = 0.095 mg/mL was isolated from Pechuel-loeschea leubnitziae leaves. Molecular docking analysis revealed that xerantholide and its analogues docked with binding affinities ranging from -5.3 to -7.4 kcal/mol and DFT predicted binding energy of -16.5 to – 43.1 kcal/mol for these sesquiterpene lactones. Based on the docking results, binding of these compounds to NgCA involves hydrogen bonding, ligand-metal-acceptor, and hydrophobic interactions. Using QSPR, a six descriptors model with good predictive ability (R = 0.789, R 2 = 0.623, AdjR2 = 0.578, BIC = 241, AIC = 225) was developed. Finally, a PASS analysis showed that these compounds are potential antibacterial agents. The results in this study suggest that the studied sesquiterpene lactones offer potential anti-gonococcal and inhibitory activity towards NgCA, thus further in-vitro studies are recommended.