A DFT and molecular docking study of xerantholide and its interaction with Neisseria gonorrhoeae carbonic anhydrase.

Xerantholide is a sesquiterpene lactone that has anti-gonorrhea and anti-plasmodium activities. We present gas-phase electronic structure calculations of the equilibrium geometry of xerantholide, its adiabatic electron affinity (AEA), adiabatic ionization energy (AIE) and the energy barrier (ΔE‡) connecting the lowest energy conformers of the sesquiterpene. The computations were performed with the B3LYP, M06-2X and ωB97xd variants of the density functional theory (DFT) in conjunction with large basis sets. With the inclusion of the vibrational zero point energy, the computed AEA range from 0.740 eV [B3LYP/Aug-CC-pVTZ] to 0.774 eV [B3LYP/6-311++G(d,p)], and the AIE is roughly 8.6 eV at all theoretical levels. At the B3LYP/Aug-CC-pVTZ level, the barrier (ΔE‡) connecting the two lowest energy conformers is predicted to be 13.9 kcal/mol. Based on the molecular docking analysis, xerantholide interacts with the active site of Neisseria gonorrhoeae carbonic anhydrase (NgCA) via hydrogen bonding, metal-acceptor interaction, and non-polar alkyl and pi-alkyl interactions. The predicted binding affinity of - 6.8 kcal/mol compares well with those obtained for standard NgCA inhibitors such as acetazolamide (-5.7 kcal/mol). A biomimetic model study involving xerantholide and zinc-tris imidazole ([ZnIm3]2+) ion was also carried out at different theoretical levels to estimate the interaction energy for the formation of the complex formed between the ligand and the active site model of NgCA. The binding free energy (ΔG) has been calculated to be - 28.5 kcal/mol at the B3LYP/6-311++G(d,p) level. The interaction mode observed in both the docking and the model calculations involves the lactone ring.

Oral hygiene in Namibia: A case of chewing sticks.

ETHNOPHARMACOLOGICAL RELEVANCE: Chewing sticks have served as the primary form of dental care for rural communities in resource-poor settings for millennia. They are one of the most important under-researched, non-timber forest products in Namibia. This review provides an overview of plants that are used as chewing sticks in Namibia and highlights pharmacological as well as phytochemical studies conducted on them. AIM OF THE STUDY: This review aims to present a summary of studies that have been done on the ethnomedicinal uses, phytochemistry, biological activity as well as evidence on the scientific validation and geographical distribution of chewing sticks in Namibia. It also highlights research gaps and provides an impetus for the scientific investigations of these plant species. MATERIAL AND METHODS: Literature searches using keywords including oral hygiene, chewing sticks, ethnomedicinal uses, phytochemistry, antimicrobial, antioxidants, anti-inflammatory activities and toxicity studies, chewing sticks, and distribution in Namibia on various electronic search engines was conducted. RESULTS: Of the 41 plant species identified, Cordia sinensis Lam., Faidherbia albida (Delile) A.Chev. and Harpagophytum zeyheri Decne. are used for both gargling and as mouthwash. The plant families Fabacae, Ebenaceae, and Burseraceae account for 22.0%, 12.2%, and 7.30% of plant species recorded as chewing sticks in Namibia respectively. This study revealed a significant relationship between plant family and scientific validation. Species belonging to Burseraceae, Apocynaceae, Montiniaceae, and Cucurbitaceae families have only been partially validated. The Kunene region, home to the Ovahimba ethnic group, had the highest proportion (87.8%) of chewing sticks species compared to other regions. CONCLUSION: This review revealed that most of the plants used as chewing sticks in Namibia require an in-depth pharmacological and phytochemical investigation as deduced from the paucity of literature on the therapeutic methods, mechanisms of action, efficacy, toxicity, and clinical relevance of these species.