Ligand-protein interactions of plant-isolated (9z,12z)-octadeca-9,12-dienoic acid with Β-ketoacyl-Acp synthase (KasA) in potential anti-tubercular drug designing.

Mycobacterium tuberculosis remains one of the world's contributors to mortality. With the emergence of SARS-CoV-2 coinfections, patients with TB are predisposed to being more heavily weighed down by COVID-19 disease and its opportunistic coinfections. The severity of the disease coupled with drug resistance on the currently used drugs warrants for the search for alternative remedies from synthetic agents, semisynthetics and natural products that include plants. Africa is rich in plant diversity with a promise as sources of drug agents, one of which is Eichhornia crassipes. This work aimed at isolating a fatty acid and dock it to ß-ketoacyl-ACP synthase for possible anti-TB drug development prospects using computational tools. (9z,12z)-Octadeca-9,12-dienoic acid was isolated from Eichhornia crassipes for the first time using chromatographic techniques and identified using 1D and 2D NMR spectroscopic methods (1H NMR, COSY, HSQC, HMBC and 13C NMR). The compound was then docked to ß-ketoacyl-ACP synthase (KasA), an essential member of the b-ketoacyl synthases encoded in the M. tuberculosis genome in comparison with its co-crystallized ligand JSF-3285, also for the first time. (9z,12z)-Octadeca-9,12-dienoic acid interacted with only phenylalanine239 and proline201 while JSF-3285 interacted with proline201, glutamine120, alanine119, leucine116, glutamine199, histadine345, phenylalanine239, glycine240 and glycine200. (9z,12z)-Octadeca-9,12-dienoic acid had a ligand efficiency of 0.24, compared to the co-crystallized ligand's 0.36. The compound was too flexible and elongated with -4.72 KCalmol-1 binding energy. Despite some unfavourable physico-chemical properties, the compound still provides reliable interactions that only require logical structural modifications by the addition of polar regions amongst others to increase interactions and ligand efficiency, which can consequently stand to be a better potential drug lead. For the first time, plant-based (9z,12z)-Octadeca-9,12-dienoic acid isolated from Eichhornia crassipes was shown to interact fairly well with ß-ketoacyl-ACP synthase and proved to be a potential starting material from which anti-tubercular drugs can be designed.

Structural and In Silico Characterization of Small Molecules Isolated from Eichhornia crassipes.

Eichhornia crassipes has been reported to have various medicinal properties including anticancer activities. The plant was collected from the Shire river in Malawi, and two cytotoxic compounds, benzene-1,4-diol and nonanedioic acid, were isolated and characterized for the first time in the leaves and roots of the plant. 1H NMR, COSY, HSQC, HMBC, 13-C, and LCMS spectroscopic experimental techniques were used to identify the compounds in their pure forms. In silico experiments showed that both compounds do not have AMES toxicity and do not inhibit cytochrome P450 enzymes, but nonanedioic acid acts as a CYP2D6 substrate. This work showed that Eichhornia crassipes can be considered to have a role as a source of potential hits and leads to drug development that can be rationally optimized for drugs.