Targeting allosteric sites of human aromatase: a comprehensive in-silico and in-vitro workflow to find potential plant-based anti-breast cancer therapeutics

Hani A. Alhadrami, Ahmed M. Sayed, Sami A. Melebari, Asem A. Khogeer, Wesam H. Abdulaal, Mohamed B. Al-Fageeh, Mohammad Algahtani, Mostafa E. Rateb*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Recent findings suggested several allosteric pockets on human aromatase that could be utilised for the development of new modulators able to inhibit this enzyme in a new mechanism. Herein, we applied an integrated in-silico-based approach supported by in-vitro enzyme-based and cell-based validation assays to select the best leads able to target these allosteric binding sites from a small library of plant-derived natural products. Chrysin, apigenin, and resveratrol were found to be the best inhibitors targeting the enzyme’s substrate access channel and were able to produce a competitive inhibition with IC50 values ranged from 1.7 to 15.8 µM. Moreover, they showed a more potent antiproliferative effect against ER+ (MCF-7) than ER- one (MDA-MB-231) cell lines. On the other hand, both pomiferin and berberine were the best hits for the enzyme’s haem-proximal cavity producing a non-competitive inhibition (IC50 15.1 and 21.4 µM, respectively) and showed selective antiproliferative activity towards MCF-7 cell lines.

Original languageEnglish
Pages (from-to)1334-1345
Number of pages12
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Issue number1
Early online date17 Jun 2021
Publication statusE-pub ahead of print - 17 Jun 2021


  • allosteric inhibition
  • anti-breast cancer
  • aromatase
  • in silico
  • natural products


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