In silico molecular docking, DFT, and toxicity studies of potential inhibitors derived from Millettia dielsiana against human inducible nitric oxide synthase

Inducible nitric oxide synthase is known as a potential biological target that plays a crucial role in regulating the release of nitric oxide and is responsible for the amount of nitric oxide released during the inflammation process. Searching for compounds from natural sources that inhibit inducible nitric oxide synthase may reduce excessive nitric oxide production and counteract metabolic diseases originating from prolonged inflammation. One of the valuable medicinal plants with significant anti-inflammatory activity evaluated in this study is Millettia dielsiana. The current work focuses on the molecular docking analysis of compounds derived from Millettia dielsiana to identify potential candidates against the inducible nitric oxide synthase enzyme. As a result, four compounds (D10 (Tupichinol C), D20 (Durmillone), D46 (Glycitin), and D50 (5,7,4′-trihydroxyisoflavone 7-O-β-d-apiofuranosyl-(1→6)-β-d-glucopyranoside) with the most potent inhibitory potential were identified with binding affinities less than −9.0 kcal mol−1. Moreover, toxicity predictions using the ProTox II web server indicated that these compounds exhibit low toxicity (Toxicity Class of 5). Compound D50 showed no activity in hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. Density functional theory was employed for molecular description, electronic properties, and chemical reactivity of the compounds. These findings provide a basis for further in-depth biological experiments in the future.