Design, Synthesis, Anticancer Evaluation and Molecular Modeling of Novel Estrogen Derivatives
Abd El-Galil E. Amr,
Elsayed A. Elsayed,
Mohamed A. Al-Omar,
Hanan O. Badr Eldin,
Eman S. Nossier,
Mohamed M. Abdallah
Affiliations
Abd El-Galil E. Amr
Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Elsayed A. Elsayed
Zoology Department, Bioproducts Research Chair, Faculty of Science, King Saud University, Riyadh 11451, Saudi Arabia
Mohamed A. Al-Omar
Pharmaceutical Chemistry Department, Drug Exploration & Development Chair (DEDC), College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Hanan O. Badr Eldin
Chemistry Department, Faculty of Science, King Khalid University, MahailAsir 61421, Saudi Arabia
A series of estrone derivatives 3–8 was designed and synthesized using estrone arylmethylenes 2a,b as starting materials and their structures were confirmed by different spectral data and elemental analyses. All the newly synthesized compounds exhibited potent in vitro and in vivo cytotoxic activities against breast cancer cell lines. In addition, all compounds were subjected to in vitro and in vivo inhibition assays for EGFR and VEGFR-2 kinases as well as p53 ubiquitination activity to obtain more details about their mechanism of action. Based on the promising results, a molecular docking study was investigated for the most representative compound 5a against the two targets, EGFR and VEGFR-2 kinases, to assess its binding affinity, hoping to rationalize and obtain potent anticancer agents in the future.
