A novel pregnene analogs: synthesis, cytotoxicity on prostate cancer of PC-3 and LNCPa-AI cells and in silico molecular docking study

被引：6

作者：

Abdul-Rida, Nabeel A. ^{[1
]}

Farhan, Ali M. ^{[1
]}

Al-Masoudi, Najim A. ^{[2
]}

Saeed, Bahjat A. ^{[3
]}

Miller, Dannah ^{[4
]}

Lin, Ming-Fong ^{[5
]}

机构：

[1] Univ Al Qadisiya, Dept Chem, Coll Sci, Al Qadisiya, Iraq

[2] Univ Basrah, Dept Chem, Coll Sci, Basrah, Iraq

[3] Univ Basrah, Dept Chem, Coll Educ Pure Sci, Basrah, Iraq

[4] Univ Colorado Anschutz Med Campus, Dept Pharmacol, Aurora, CO 80045 USA

[5] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, 985870 Nebraska Med Ctr, Omaha, NE 68198 USA

来源：

MOLECULAR DIVERSITY | 2021年 / 25卷 / 02期

关键词：

Amides; Anticancer activity; Molecular docking study; Oxadiazole; Pregnene analogs; Pyrazole; HYDROXYLASE INHIBITION-ACTIVITY; CYP17; INHIBITORS; ANTITUMOR-ACTIVITY; COSALANE ANALOGS; DERIVATIVES; PHARMACOKINETICS; PROLIFERATION; ABIRATERONE; SURVIVAL; THERAPY;

D O I：

10.1007/s11030-020-10038-w

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：

New pregnene analogs of N-hydroxamic acid 6, imino-propane hydrazides 7 and 8 as well as the aryl amides 9-11, oxadiazole, pyrazole and sulfinyl analogs 13-15, via the hydrazide analog 5 of methyl ((5-pregnen-3 beta,17 beta-diol-15 alpha-yl)thio)propanoate (4) were synthesized. The in vitro cytotoxic activities of selected synthesized steroids against two human prostate cancer cell lines (PC-3, and LNCaP-AI) were evaluated by MTT assay. Compound 10 was the most active cytotoxic agent among these steroids against PC-3 and LNCaP-AI cell lines with inhibition of 96.2%, and 93.6% at concentration levels of 10.0 mu M and 91.8%, and of 79.8% at concentration of 1.0 mu M, respectively. Molecular docking study of 10 showed a hydrogen bonding with the amino acid Asn705 residue of the receptor 1E3G, together with hydrophobic interactions. Therefore, compound 10 can be considered as a promising anticancer agent due to its potent cytotoxic activity. Graphic abstract

引用

页码：661 / 671

页数：11

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