| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2027498 | Steroids | 2016 | 10 Pages |
•Several heterocyclic and curcumin-steroid derivatives were synthesized and confirmed.•Evaluation of the cytotoxicity against breast cancer cell lines (MCF-7).•The expression levels of CCND1, Survivin, BCL-2, CDC2, P21 and P53, genes were investigated.•This study introduced promising pro-apoptotic anticancer agents.
Anticancer agents consisting of hybrid molecules are used to improve effectiveness and diminish drug resistance. The current study aimed to introduce newly synthesized hetero-steroids of promising anticancer effects. Besides, the pro-apoptotic effects of new compounds were investigated extensively. Several pyrimidino-, triazolopyrimidino-, pyridazino-, and curcumin-steroid derivatives were synthesized, elucidated and confirmed using the spectral and analytical data. The synthesized hetero-steroids, compounds 9, 10, 11, 12, 13, 14, 15, 18, 20, 21, 22 and 24, were tested for their cytotoxic effects versus human breast cancer cells (MCF-7) using neutral red supravital dye uptake assay. Compound 24 (IC50 = 18 μM) showed more inhibitory influence on MCF-7 growth. Using QRT-PCR (Quantitative real time-polymerase chain reaction), CCND1, Survivin, BCL-2, CDC2, P21 and P53, genes expression levels were investigated. The study results disclose that compounds 4, 7, 18, 24 knocked down the expression levels of CCND1, Survivin, BCL-2 and CDC2. However, P21 and P53 were up-regulated by compounds 21, 22. This study introduced promising pro-apoptotic anticancer agents acting through the modulation of key regulators of apoptosis and cell cycle genes.
Graphical abstractThe present study aimed to introduce newly synthesized steroid and curcumin derivatives of promising anticancer effects. The pro-apoptotic effects of these compounds were investigated extensively. Compounds 21, 22, 24 are the most promising as pro-apoptotic anticancer agents acting through the regulation of key regulators of apoptosis and cell cycle genes.Figure optionsDownload full-size imageDownload as PowerPoint slide
