Rotenoid Derivatives from 𝑨𝒎𝒐𝒓𝒑𝒉𝒂 𝒇𝒓𝒖𝒕𝒊𝒄𝒐𝒔𝒂: 𝑰𝒏 𝒗𝒊𝒕𝒓𝒐 and 𝑰𝒏 𝑺𝒊𝒍𝒊𝒄𝒐 Studies against Tyrosine Kinase Receptors

Amorpha fruricosa contains flavonoids, rotenoids, and stilbenoids, which are the primary bioactive compounds found in these species. These organisms are a rich source of secondary metabolites. In this study, two known rotenoids, tephrosine (۱) and ۶′-O--D-glucopyranosil-dalpanol (۲), were successfully isolated from the seed extract of A. fructicosa. The isolated compounds were characterized using ۱D and ۲D NMR, mass spectrometry (MS), and circular dichroism (CD). Compounds ۱ and ۲ was evaluated for its inhibitory activity against eight receptor tyrosine kinases (EGFR, HER۲, HER۴, IGF۱R, InsR, KDR, PDGFRα, and PDGFRβ). Compound ۲ exhibited moderate EGFR inhibitory activity. Molecular docking and dynamics simulations were performed for compound ۲ by targeting the binding pocket of EGFR. Molecular docking results revealed that the glycoside and methoxy groups exhibited hydrogen bond interactions with Glu۸۰ and Thr۸۳۰, whereas other interactions were dominated by van der Waals (Vdw), π-σ, and π-alkyl interactions with the rotenoid skeleton. Moreover, molecular dynamics (MD) simulations demonstrated that molecular complexation between compound ۲ and EGFR was stable. Analysis of the ۳D structure of the minimal MD energy of compound ۲ revealed hydrogen bonding between the carbonyl group and Met۷۶۹. These findings suggest that compound ۲ holds promise as a lead compound for further development as an EGFR-targeting anticancer agent.

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𝐴𝑚𝑜𝑟𝑝ℎ𝑎 𝑓𝑟𝑢𝑡𝑖𝑐𝑜𝑠𝑎 ، Receptor tyrosine kinases ، Anti-cancer agent ، MD Simulations