Synthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives

Determination of 17α-hydroxylase-C17,20-lyase (P45017α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

“…various laboratory techniques have been developed in the latest decades for the investigation of 17α-hydroxylase and C 17,20 -lyase activities of the P450 17α . biotransformations are more often monitored via conversion of 3 h or 14 C labelled substrate steroids. following the enzyme reaction labelled product steroids are isolated with chromatography and then quantified by radiometric detection [3, 6, 10-11, 21-22, 29, 40].…”

“…using these methods we have studied inhibitory action of selected steroidal 17-picolyl and 17-picolinylidene derivatives exerted towards the rat P450 17α . earlier publications describe synthesis methods and chemical properties of these compounds [7,14,25]. …”

Steroidal Inhibitors of CYP17A1 as a Template For Novel Anti-Cancer Agents Development

“…16-Кетоаналоги 289 и 290 подавляли активность СYP17A1 примерно с той же эффективностью, что и 16-незамещённые производные 279 и 281, и проявляли сильную токсичность в клетках миелоидного лейкоза линии K562 [62]; данные об активности в клетках карциномы простаты отсутствуют (формула 29).…”

Recent developments in steroidal and nonsteroidal aromatase inhibitors for the chemoprevention of estrogen-dependent breast cancer

“…Biological activity data revealed that 17-picolinylidene-16-one derivatives were more potent AIs than 17-picolyl and 17-picolinylidene derivatives, and compound 8 (Fig.2.) was the most effective inhibitor of aromatase (93.3% inhibition). [26] The presence of a cyano group in the non-steroidal AIs letrozole and anastrozole suggested the introduction of cyano functionality in the D ring, and several compounds with a 17-methyl-16,17-seco-16-nitrile-17-one moiety, with 1,4-diene-3-on, 4,6-dien-3-on, 1,4,6-trien-3-on, and 4-hydroxy-4-en-3-one systems, were synthesized. Compound 9 (Fig.2.…”

“…A number of C-6-substituted 2-alkynyloxy compounds exhibited promising aromatase inhibiton activity. The most potent compound was a 2-pentynyl oxy derivative (26) (Fig.3. ), with an IC 50 = 0.012 µM.…”