title: Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents.
abstract: Anti-cancer agents which combine two biologically active compounds in one such as steroidal heterocyclic derivatives attain both hormone and cytotoxic effects on cancer cells. The aim of the present study is to synthesize and evaluate new potential chemotherapeutic anti-breast cancer agents. Several pyridazino-, pyrimido-, quinazolo-, oxirano- and thiazolo-steroid derivatives were synthesized. The structure of the novel steroid derivatives was confirmed using the analytical and spectral data. The most structurally promising of the novel synthesized steroid derivatives, compounds 8, 12, 17, 20, 22c, 24c, 30a and 30b, were investigated individually as anti-breast cancer agents against human breast cancer cells (MCF-7) using sulforhodamine B (SRB) assay. The tested compounds 17, 20, 22c and 8 showed potent broad spectrum cytotoxic activity in vitro after 48 h incubation. Compound 17 (IC(50)=2.5 μM) exhibited more inhibitory influence on MCF-7 growth than the reference drug doxorubicin (Dox) (IC(50)=4.5 μM) after 48 h incubation. Also, the present study showed that all the tested steroid derivatives exhibited significant depletion with various intensities in gene expression of breast cancer related genes (VEGF, CYP19 and hAP-2γ). Noteworthy, compounds 17, 20 and 22c showed the most pronounced effect in this respect.
authors: Hormones Department, National Research Centre, Dokki, Giza, Egypt. gamalae@hotmail.com
authors: Gamal A
authors: GA
authors: Elmegeed
authors: Wagdy K B
authors: WK
authors: Khalil
authors: Rafat M
authors: RM
authors: Mohareb
authors: Hanaa H
authors: HH
authors: Ahmed
authors: Mervat M
authors: MM
authors: Abd-Elhalim
authors: Ghada H
authors: GH
authors: Elsayed
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001141:Aromatase / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D020128:Inhibitory Concentration 50; D013256:Steroids / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D050656:Transcription Factor AP-2 / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids; C493679:TFAP2C protein, human; D050656:Transcription Factor AP-2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D001141:Aromatase