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

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.