Vasorelaxant effect of a phenylethylamine analogue based on schwarzinicine A an alkaloid isolated from the leaves of Ficus schwarzii

• Main Authors: Govindaraju, Kayatri, Mak, Yin Ying, Lee, Fong Kai, Bauer, Claudia C., Lim, Kuan Hon, Bon, Robin S., Kong, Cin, Then, Sue Mian, Ting, Kang Nee
• Format: Article
• Published: Elsevier 2024
• Subjects: R Medicine; RS Pharmacy and materia medica
• Online Access: http://eprints.um.edu.my/44247/; https://doi.org/10.1016/j.phytol.2023.11.007

N-Phenethyl-1-phenyl-pentan-3-amine (1) is a new compound synthesised as a simplified analogue of schwarzinicine A (2), a natural compound extracted from Ficus schwarzii. Compound 1 differs from compound 2 due to its structural simplification, featuring two phenyl rings without methoxy substitution, as opposed to compound 2, which possesses three 3,4-dimethoxy aromatic rings. Our previous research findings highlighted the calciuminhibitory effects of compound 2, but the mechanism of action for compound 1 remains unexplored, serving as the primary focus of this study. Building upon our earlier research, this study aimed to elucidate compound 1's calcium-modulating potential by using rat-isolated aortae in an organ bath set-up and HEK cells expressing hTRPC channels with the fluorometric assay to measure calcium influx. Compound 1 elicited a vasorelaxation response (Emax 111.4%) similar to its parent compound 2 (Emax 123.1%), and inhibited hTRPC3-, hTRPC4-, hTRPC5-, and hTRPC6-mediated calcium influx into HEK cells with IC50 values of 6, 2, 2, 5 mu M, respectively. Compound 1 has a similar pharmacological profile as its parent compound 2, whereby it exerts a vasorelaxant effect by attenuating calcium influx and inhibits multiple TRPC channels.