17(E)-Picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies

Ajduković, Jovana J.; Djurendić, Evgenija A.; Petri, Edward T.; Klisurić, Olivera R.; Ćelić, Andjelka; Sakač, Marija N.; Jakimov, Dimitar; Gaši, Katarina M. Penov

doi:10.1016/j.bmc.2013.09.063

Cited by 33 publications

(26 citation statements)

References 30 publications

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“…the rigid planar structure of our 17-picolinylidene groups, in particular, stabilizes the nitrogen in a position which is preferred for co-ordination to the heme of the enzyme [1]. Double bond at C17-C20 in the 17-picolinylidene compounds extends π-electron conjugation of the heterocyclic aromatic ring.…”

Section: Discussionmentioning

confidence: 99%

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Szabó

Ajduković

Djurendić

et al. 2015

Acta Biologica Hungarica

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17α-hydroxylase-C 17,20 -lyase (P450 17α ) is a key regulator enzyme of the steroid hormone biosynthesis in both the adrenals and the testes. inhibition of this enzyme can block androgen synthesis in an early step, and may thereby be useful in the treatment of several androgen-dependent diseases. We developed radiosubstrate in vitro incubation methods for the determination of the distinct 17α-hydroxylase and C 17,20 -lyase activities of the enzyme using rat testicular homogenate as enzyme source. With this method we have studied the inhibiting activity of selected steroidal picolyl and picolinylidene compounds. tests revealed a substantial inhibitory action of the 17-picolinyliden-androst-4-en-3-one compound.

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Section: Discussionmentioning

confidence: 99%

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Szabó

Ajduković

Djurendić

et al. 2015

Acta Biologica Hungarica

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“…Соединения 281, 283, 286 и 287 умеренно подавляли пролиферацию клеток карциномы простаты РС-3 и слабо -клеток карциномы молочной железы MCF-7 [59,60], однако соединения 279 и 282 сильно подавляли пролиферацию и вызывали апоптоз в клетках карциномы молочной железы MDA-MB-231 [61] (формула 28).…”

Section: формула 24unclassified

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

Latysheva

Misharin

2018

BMCRM

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This review deals with studies of researches of novel CYP17A1 steroidal inhibitors and relative compounds published over the last ten years. The review contains six chapters in which novel targets of well-known CYP17A1 inhibirors (abiraterone and galeterone), anti-cancer and anti-proliferative activities of them major metabolites and new synthetic analogs, and in addition another nitrogen-containing androstane and pregnane derivatives are considered. In the review 354 structures of novel steroid derivatives and them anti-cancer efficiency data are considered. Analysis of the literature data allows us to consider steroidal inhibitors of CYP17A1 as multi-target anti-cancer agents with high pharmacological potential.

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“…1); благодаря сопряжению двух двойных связей [17(20) и C=N] стероидный фрагмент и оксазолиновый (в соединениях 1, 3 -6) или бензоксазоловый (в соединении 2) цикл лежат в одной плоскости. Для каждого из соединений существуют два (примерно равных по энергии) стабильных конформера, различающихся значением двугранного угла C 20-C2' и соответствующих син-и анти-ориентации двойных связей 17 (20) и C=N [18] (значения двугранного угла C 20-C2' для син-и анти-конформеров составляют 0°и ~ 180°, соответственно [16]). Для соединений с ассимметрическим центром при С4' (3 и 4) 4'-гидроксиметильный заместитель выведен из плоскости молекулы и должен располагаться или над, или под этой плоскостью в зависимости от конфигурации хирального центра С4' и величины двугранного угла C 20-C2' .…”

Section: результаты и обсуждениеunclassified

“…Ранее было показано, что 2'-{[(E)-3b-гидроксиандрост-5-ен-17-илиден]-метил}-4',5'-дигидро-1',3'-оксазол 1 связывается с рекомбинантным препаратом CYP17A1 и ингибирует каталитическую активность фермента подобно абиратерону [17]. В работе [18] [2][3][4][5][6][7][8][9][10][11][12][13].…”

Section: Introductionunclassified

Interaction of novel oxazoline derivatives of 17(20)e-pregna-5,17(20)-diene with cytochrome P450 17A1

et al. 2016

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In order to find novel inhibitors of 17a-hydroxylase-17,20-lyase (cytochrome P450 17A1, CYP17A1), a key enzyme of biosynthesis of androgens, molecular docking of six new oxazoline-containing derivatives 17(20)E-pregna-5,17(20)-diene has been carried out to the active site of the crystal structure of CYP17A1 (pdb 3ruk). Results of this study indicate that: 1) complex formation of docked compounds with CYP17A1 causes their isomerization in energetically less favorable 17(20)Z-isomer; 2) the localization of the steroid moiety of all compounds in the active site is basically the same; 3) the structure of the oxazoline moiety significantly influences its position relative to heme as well as the energy of complex formation; 4) coordination of the nitrogen atom of the oxazoline moiety and the heme iron is only possible in the 17(20)Z-conformation with anti oriented double bonds 17(20), and C=N; 5) the presence of two substituents at C4' of the oxazoline moiety significantly impairs ligand binding; 6) oxazoline - and benzoxazole-containing derivatives 17(20)E-pregna-5,17(20)-diene can effectively inhibit the catalytic activity CYP17A1 and may be of interest as a basis for the development of new drugs for the treatment of androgen-dependent cancer.

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17(E)-Picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies

Cited by 33 publications

References 30 publications

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

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

Interaction of novel oxazoline derivatives of 17(20)e-pregna-5,17(20)-diene with cytochrome P450 17A1

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17(E)-Picolinylidene androstane derivatives as potential inhibitors of prostate cancer cell growth: Antiproliferative activity and molecular docking studies

Cited by 33 publications

References 30 publications

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

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

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

Interaction of novel oxazoline derivatives of 17(20)e-pregna-5,17(20)-diene with cytochrome P450 17A1

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Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds

Determination of 17α-hydroxylase-C_17,20-lyase (P450_17α) enzyme activities and their inhibition by selected steroidal picolyl and picolinylidene compounds