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

被引：28

作者：

Ajdukovic, Jovana J. ^{[1
]}

Djurendic, Evgenija A. ^{[1
]}

Petri, Edward T. ^{[3
]}

Klisuric, Olivera R. ^{[2
]}

Celic, Andjelka S. ^{[3
]}

Sakac, Marija N. ^{[1
]}

Jakimov, Dimitar S. ^{[4
]}

Gasi, Katarina M. Penov ^{[1
]}

机构：

[1] Univ Novi Sad, Fac Sci, Dept Chem Biochem & Environm Protect, Novi Sad 21000, Serbia

[2] Univ Novi Sad, Fac Sci, Dept Phys, Novi Sad 21000, Serbia

[3] Univ Novi Sad, Fac Sci, Dept Biol & Ecol, Novi Sad 21000, Serbia

[4] Oncol Inst Vojvodina, Novi Sad 21204, Serbia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2013年 / 21卷 / 23期

关键词：

Androstane; 17 alpha-Picolyl and 17(E)-picolinylidene derivatives; Synthesis; Antiproliferative activity; Antitumor; Virtual screening; Molecular docking; BIOLOGICAL EVALUATION; ANTITUMOR-ACTIVITY; 17-PICOLYL; PHARMACOKINETICS; DETERMINANTS; INDUCTION; ESTROGEN; DESIGN;

D O I：

10.1016/j.bmc.2013.09.063

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report a rapid and efficient synthesis of A-ring modified 17 alpha-picolyl and 17(E)-picolinylidene androstane derivatives from dehydroepiandrosterone. Compounds were validated spectroscopically and structurally characterized by X-ray crystallography. Virtual screening by molecular docking against clinical targets of steroidal anticancer drugs (ER alpha, AR, Aromatase and CYP17A1) suggests that 17(E)-picolinylidene, but not 17 alpha-picolyl androstanes could specifically interact with CYP17A1 (17 alpha-hydroxylase) with similar geometry and affinity as Abiraterone, a 17-pyridinyl androstane drug clinically used in the treatment of prostate cancer. In addition, several 17(E)-picolinylidene androstanes demonstrated selective antiproliferative activity against PC3 prostate cancer cells, which correlates with Abiraterone antiproliferative activity and predicted CYP17A1 binding affinities. Based on these preliminary results, 17(E)-picolinylidene androstane derivatives could be a promising starting point for the development of new compounds for the treatment of prostate cancer. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：7257 / 7266

页数：10

共 37 条

[1]

Agilent, 2010, AG TECHN YARNT OXF C

[2] SIR97:: a new tool for crystal structure determination and refinement [J].

Altomare, A ;

Burla, MC ;

Camalli, M ;

Cascarano, GL ;

Giacovazzo, C ;

Guagliardi, A ;

Moliterni, AGG ;

Polidori, G ;

Spagna, R .

JOURNAL OF APPLIED CRYSTALLOGRAPHY, 1999, 32 :115-119

[3] 17α-Hydroxylase/17,20 lyase inhibitor VN/124-1 inhibits growth of androgen-independent prostate cancer cells via induction of the endoplasmic reticulum stress response [J].

Bruno, Robert D. ;

Gover, Tony D. ;

Burger, Angelika M. ;

Brodie, Angela M. ;

Njar, Vincent C. O. .

MOLECULAR CANCER THERAPEUTICS, 2008, 7 (09) :2828-2836

[4]

David-Beabes GL, 2000, INT J ONCOL, V17, P1077

[5] Comparison of crystal structures of human androgen receptor ligand-binding domain complexed with various agonists reveals molecular determinants responsible for binding affinity [J].

De Jesus-Tran, KP ;

Cote, PL ;

Cantin, L ;

Blanchet, J ;

Labrie, F ;

Breton, R .

PROTEIN SCIENCE, 2006, 15 (05) :987-999

[6] Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001 [J].

DeVore, Natasha M. ;

Scott, Emily E. .

NATURE, 2012, 482 (7383) :116-U149

[7] Synthesis of some epoxy and/or N-oxy 17-picolyl and 17-picolinylidene-androst-5-ene derivatives and evaluation of their biological activity [J].

Djurendic, Evgenija ;

Daljev, Jouana ;

Sakac, Marija ;

Canadi, Janos ;

Santa, Suzana Jovanovic ;

Andric, Silvana ;

Klisuric, Olivera ;

Kojic, Vesna ;

Bogdanovic, Gordana ;

Djurendic-Brenesel, Maja ;

Novakovic, Sladjana ;

Gasi, Katarina Penov .

STEROIDS, 2008, 73 (01) :129-138

[8] Synthesis and cytotoxic activity of some 17-picolyl and 17-picolinylidene androstane derivatives [J].

Djurendic, Evgenija A. ;

Ajdukovic, Jovana J. ;

Sakac, Marija N. ;

Csanadi, Janos J. ;

Kojic, Vesna V. ;

Bogdanovic, Gordana M. ;

Gasi, Katarina M. Penov .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2012, 54 :784-792

[9]

Farrugia L. J., 1999, Journal of Applied Crystallography, V32, P837, DOI [DOI 10.1107/S0021889812029111, 10.1107/S0021889899006020, DOI 10.1107/S0021889899006020]

[10]

Gasi K.M, 2010, ACTA PERIOD TECHNOL, V41, P169

← 1 2 3 4 →