Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line

Cortés‐Benítez, Francisco; Cabeza, Marisa; Ramírez‐Apán, María Teresa; Alvarez-Manrique, Berenice; Bratoeff, Eugene

doi:10.1016/j.ejmech.2016.05.059

Cited by 11 publications

(2 citation statements)

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“…Azasteroidal compounds target a variety of biological processes and therefore are potential candidates for the treatment of a large group of diseases, including breast and prostate cancers (PCas), benign prostatic hyperplasia (BPH), osteoporosis, and autoimmune diseases [1e4]. PCa is one of the most frequent malignant tumors in the world and is the second leading cause of death in men [5,6]. The androgen receptor (AR) signaling pathway plays an important role in PCa development and progression.…”

Section: Introductionmentioning

confidence: 99%

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Novel 4-azaandrostenes as prostate cancer cell growth inhibitors: Synthesis, antiproliferative effects, and molecular docking studies

Brito

Santos

Almeida

et al. 2018

Comptes Rendus. Chimie

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In this study, synthesis, structural characterization, molecular docking studies, and antiproliferative effects in four different cell lines of several novel 16-arylidene-4-azaandrost-5-ene compounds are reported. These compounds were prepared by oxidative cleavage of the enone system of androstenedione followed by an azacyclization reaction and an aldol condensation with various aldehydes at C16. In the androgen-dependent LNCaP cells, the most relevant antiproliferative effects were observed with the 16-phenyl, 16-p-tolyl, and 16-p-nitrophenyl derivatives. Compound 16E-[(4-methylphenyl)methylidene]-4azaandrost-5-ene-3,17-dione was the most potent in these cells (IC 50 ¼ 28.28 mM), having lower antiproliferative effects in the androgen-independent PC-3 cells (IC 50 ¼ 45.31 mM). In addition, an interesting selectivity toward cancer cell lines was found for all compounds because a generally low cytotoxicity was detected in healthy human fibroblasts. Furthermore, the 16-p-tolylazaandrostene steroid induced a reduction of viability in LNCaP cells similar to that observed with finasteride, a clinically used 5a-reductase inhibitor. Moreover, molecular docking studies predicted that these 4-azaandrostene derivatives can interact with 5b-reductase, which has a high level of similarity to 5areductase enzyme, and with other common targets of steroidal drugs, particularly the enzyme 17a-hydroxylase/17,20-lyase.

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Section: Introductionmentioning

confidence: 99%

“…Within the natural, semisynthetic, and synthetic steroidal derivatives with high antitumor interest [5,15], several other examples related to the present research work can be highlighted. In this context, some 17(E)picolinylidene androstane derivatives were described as potential inhibitors of prostate and breast cancer cell growth.…”

Section: Introductionmentioning

confidence: 99%