title: Synthesis of androstanopyridine and pyrimidine compounds as novel activators of the tumor suppressor protein p53.
abstract: A series of androstane derivatives 2-16 were synthesized from 3β-hydroxyandrostan-17-one derivatives (1a-e). Compounds (1a,b) were treated with ethyl cyanoacetate, cyanoacetamide, or malononitrile and gave the corresponding derivatives 2-7, respectively. Additionally, compounds (1a-e) were condensed with cyanothioacetamide, urea, or guanidine hydrochloride afforded the corresponding derivatives 8-12, which then by Moffat oxidation gave the oxidized derivatives 9, 11 and 13, respectively. Finally, compound (1) condensed with acetyl acetone or ethyl acetoacetate gave cyclohexene derivatives (14a-c) and (15a,b), respectively. Compound 15 was oxidized with a Moffat oxidizing agent and afforded the corresponding oxidized compound 16. The newly synthesized compounds activated the tumor suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2.
authors.forename: Mohamed M M
authors.initials: MM
authors.lastname: Hussein
authors.forename: Abd El-Galil E
authors.initials: Ael-G
authors.lastname: Amr
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Abdalla
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Al-Omar
authors.forename: Hany M
authors.initials: HM
authors.lastname: Safwat
authors.forename: Mohamed H
authors.initials: MH
authors.lastname: Elgamal