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Steroidal alkaloids efficient aromatase inhibitors with potential for the treatment of postmenopausal breast cancer
Author(s) -
Ali Amjad,
Jan Naeem Ullah,
Ali Safdar,
Ahmad Bashir,
Ali Abid,
Samrana Samrana,
Jahan Azra,
Ali Hamid,
Khan Imtiaz Ali,
Rahim Haroon,
Ali Ijaz,
Kifayatullah Muhammad,
Amin Fazli
Publication year - 2020
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13635
Subject(s) - aromatase , active site , chemistry , enzyme , exemestane , docking (animal) , stereochemistry , lipinski's rule of five , drug , steric effects , breast cancer , pharmacology , biochemistry , cancer , biology , medicine , in silico , genetics , nursing , gene
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 (a), Dictyophlebine (b), Sarcovagine‐D (c) and Saracodine (d) Holaphylline (e) from Sarcococca saligna to investigate the anticancer 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 IC 50 values of compound 1 and 5 were found 138.27 ± 0.01 µl and 12.91 ± 0.01 µl, 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 with the test compounds, having IC 50 values of 0.052 ± 0.01 µl. Both compounds showed favorable electrostatic interactions with the active site of aromatase enzyme but the shape and steric bulk of the compounds was 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.