The plants of Meliaceae are native to tropical and subtropical regions as the Americas, west India, Southeast Asia, and Southern China. Many species of the genera Khaya, Swietenia, Aphanamixis, and Melia in this family are known as medicinal plants and have biological activities such as antiviral, antimicrobial, antifeeding, insecticidal, and cytotoxic properties. The objectives of this research are to characterize and evaluate the bioactive limonoids from several plants of Meliaceae against phytopathogenic fungi. During the search of antifungal compounds from the plants of Meliaceae, the three methanol extracts of Melia dubia, Aphanamixis polystachya, and Swietenia macrophylla were found to suppress the mycelial growth of several phytopathogenic fungi. Nine limonoids isolated from M. dubia (1–2), A. polystachya (3–5), and S. macrophylla (6–9) were evaluated, for the first time, their antifungal effectiveness against nine phytopathogenic fungi Fusarium oxysporum, Magnaporthe oryzae, Sclerotium rolfsii, Rhizoctonia solani, Alternaria spp., and Botrytis cinerea, and three oomycetes Phytophthora species. Limonoids 2, 3, 6, and 8 displayed a remarkable broad-spectrum antifungal activity against all the test fungi. Sclerotium rolfsii was highly sensitive to the four limonoids with IC50 values ranging from 79.4 to 128.0 µg/mL. Notably, chisocheton compound G (3) isolated from A. polystachya and khayanolide B (8) isolated from S. macrophylla were the most potent antifungal limonoids and exhibited a dose-dependent activity against Phytophthora species. Compounds 2 and 9 displayed moderate activity against M. oryzae. Our study results demonstrated the discovery of antifungal and lead compounds from the group of limonoids for application in the control of fungal plant diseases.

The phytochemical constituents from the roots of Millettia speciosa were investigated by chromatographic isolation, and their chemical structures were characterized using the MS and NMR spectroscopic methods. A total of 10 compounds, including six triterpenoids, two flavonoids, and two phenolic compounds, were identified from the roots of M. speciosa. Out of the isolated compounds, eight showed inhibitory effects on NO production in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, with IC50 values ranging from 43.9 to 449.5 µg/mL. Ursane-type triterpenes significantly suppressed NO production compared to the remaining compounds. In addition, these compounds also exhibited remarkable inhibitory effects on α-glucosidase. Among the tested compounds, 4, 5, and 10 exhibited excellent α-glucosidase inhibition, with IC50 values ranging from 1.1 to 2.2 µg/mL. Almost all of the test compounds showed little or no acetylcholinesterase inhibition, except for 5, which showed moderate anti-acetylcholinesterase activity in vitro. The molecular docking study of α-glucosidase inhibition by 3–5 and 10 was conducted to observe the interactions of these molecules with the enzyme. Compounds 4, 5, and 10 exhibited a better binding affinity toward the targeted receptor and the H-bond interactions located at the entrance of the enzyme active site pocket in comparison to those of 3 and the positive control acarbose. Our findings evidence the pharmacological potential of this species and suggest that the phytochemicals derived from the roots of M. speciosa may be promising lead molecules for further studies on the development of anti-inflammatory and anti-diabetes drugs.