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Chemical biology & drug design 2019-Oct

Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of post-menopausal breast cancer.

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Amjad Ali
Naeem Jan
Safdar Ali
Bashir Ahmad
Abid Ali
Samrana Samrana
Azra Jahan
Hamid Ali
Imtiaz Khan
Haroon Rahim

Nøgleord

Abstrakt

Plant derived natural products are of great interest due to their diversity in modern drug discovery. Sarcococca saligna has been used for the treatment of different diseases. The present study was aimed at isolating phytochemical constituents including Alkaloid-C (1), Dictyophlebine (2), Sarcovagine-D (3) and Saracodine (4) Holaphylline (5) from Sarcococca saligna to investigate the anti-cancer effect of these compounds. These compounds were evaluated for inhibition of aromatase enzyme of breast cancer in assistance by molecular docking simulations to understand molecular interaction between the enzyme and ligands. The IC50 values of compound 1 and 5 were found 138.27±0.01µL and 12.91±0.01µL respectively and both were found active due to their bulky structures in comparison to the active site of aromatase enzyme. The standard drug exemestane showed potent activity in comparison to the test compounds, having IC50 values of 0.052±0.01µL. Both compounds showed favourable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds were the limiting factor in their inhibitory effects. New lead compounds could be generated after extensive modifications guided by computational and experimental tools as a possible anticancer agents by targeting aromatase enzyme.

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