Potent Anti-Ovarian Cancer with Inhibitor Activities on Both Topoisomerase II and V600EBRAF of Synthesized Substituted Estrone Candidates

Molecules

AhmedA. Fayed¹  Elsayed A. Elsayed²  Mohamed El-Naggar³  MohamedM. Abdalla⁴  AbdEl-Galil E. Amr⁴  Mohamed A. Al-Omar⁵ 

[1] Development Chair (DEDC), Pharmaceutical Chemistry Department, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Applied Organic Chemistry Department, National Research Center,Cairo 12622, Egypt;Chemistry Department, Faculty of Sciences, University of Sharjah, Sharjah 27272, UAE;;Drug Exploration &Zoology Department, Bioproducts Research Chair, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;

关键词: estrone derivatives;    hydrazine;    N-substituted pyrazoline;    anti-ovarian cancer;    topoisomerase II inhibitor;    kinase inhibitor;   

DOI  :  10.3390/molecules24112054

来源: DOAJ

【 摘 要 】

A series of 16-(α-alkoxyalkane)-17-hydrazino-estra-1(10),2,4-trien[17,16-c]-3-ol (3a−l) and estra-1(10),2,4-trien-[17,16-c]pyrazoline-3-ol derivatives (4a−d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material. Condensation of 1 with aldehydes gave the corresponding arylidine derivatives 2a,b which were treated with hydrazine derivatives in alcohols to give the corresponding derivatives 3a−l, respectively. Additionally, treatment of 2a,b with methyl- or phenylhydrazine in ethanolic potassium hydroxide afforded the corresponding N-substituted pyrazoline derivatives 4a−d, respectively. All these derivatives showed potent anti-ovarian cancer both in vitro and in vivo. The mechanism of anti-ovarian cancer was suggested to process via topoisomerase II and ^V600EBRAF inhibition.

【 授权许可】

Unknown