Abstract
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.
Highlights
IntroductionEstrone derivatives with antitumor activities must be devoid completely of the estrogenic activities [4,5,6]
Synthetic alterations of estrone lead to discovering of compounds with diverse biological activities, for example with antitumor effect [1], as anti-breast cancer agent [2] and with antioxidant activity [3].Estrone derivatives with antitumor activities must be devoid completely of the estrogenic activities [4,5,6].The inversion of the configuration at C-13 lead to estrone derivatives with antitumor activities devoid from hormonal actions due to conformational change for the overall molecule resulting from the cis junction of rings C and D [4,7]
A series of 17-hydrazino-estratrienol (3a–l) and pyrazolinestratrienol (4a–d) were synthesized from corresponding arylidines 2a,b which was prepared from estrone 1 as starting material
Summary
Estrone derivatives with antitumor activities must be devoid completely of the estrogenic activities [4,5,6]. The inversion of the configuration at C-13 lead to estrone derivatives with antitumor activities devoid from hormonal actions due to conformational change for the overall molecule resulting from the cis junction of rings C and D [4,7]. Some recent publications report on the syntheses and in vitro biological evaluation of several 13α-estrone derivatives [8,9,10,11]. These derivatives exhibited biological activities with substantial anti-proliferative or enzyme inhibitory potentials. Most literature data are mainly focusing on 13α-estrone substitution in ring D, while modified derivatives with ring A substitutions are rarely reported [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
