Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents

Elmegeed G.A.; Khalil W.K.B.; Mohareb R.M.; Ahmed H.H.; Abd-Elhalim M.M.; Elsayed G.H.

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Cytotoxicity and gene expression profiles of novel synthesized steroid derivatives as chemotherapeutic anti-breast cancer agents

Elmegeed G.A.; Khalil W.K.B.; Mohareb R.M.; Ahmed H.H.; Abd-Elhalim M.M.; Elsayed G.H.

Full Text link: https://t.ly/lW7JL

Date issued: 2011

Doi: https://doi.org/10.1016/j.bmc.2011.09.033 PubMed ID 22000946

Series Info: Bioorganic and Medicinal Chemistry
19

Type: Conference Paper

Keywords: Breast cancer , Cytotoxicity , Gene expression , Heterocycles , Steroids , 17 [4'(1h) oxo 3' phenyl 2' thioxoquinazolin 1 yl]androst 4 en 3 one , 17 chloroandrost 4 en 3 one , 2 (3beta acetoxy 5alpha androstan 17 ylideneamino) 4 (methylthio)butanoic acid , 2 (3beta acetoxy 5alpha androstan 17 ylideneamino) 4 (methythio)butanoic acid , 2' (3 oxoandrost 4 en 17 yl amino) 5' fluorobenzoic acid , 2' (3 oxoandrost 4 en 17 yl amino)benzoic acid , 3' acetylspiro[oxiran 2',17beta 5alpha androstan] 3beta ol , 3' acetylspiro[oxiran 2',3beta andros 4 en] 17beta ol , 3' benzoyl spiro[oxiran 2',17beta 5 alpha androstan] 3beta ol , 3' benzoylspiro[oxiran 2',3beta andros 4 en] 17beta ol , 3' benzoylspiro[oxiran 2',3beta androst 4 en] 17beta ol , 3beta acetoxy 1',3' thiazolo[4',5',:17,16] 5alpha androstan 2' acetonitrile , 3beta acetoxy 16 bromo 5alpha androstan 17 one , 3beta acetoxy 17 ylideneamino(1',4',5',6' tetrahydro 3' hydroxypyridazin 4' yl) 5alpha androstane , 3beta acetoxy 17 ylideneamino(n 2' pyrimidylbenzenesulfonamide) 5alpha androstane , 3beta acetoxy 17 ylideneamino(n 2' pyrimidylbenzenesulfonamidesodium) 5alpha androstane , 3beta acetoxy 17 ylideneamino[2' (n 2inch pyrimidylbenzenesulfonamide)ethanol] 5alpha androstane , 3beta acetoxy 2' amino 1',3' thiazolo[4',5':17,16] 5alpha androstane , 3beta acetoxy n (diethylenetriamine)copper(II)dinitrite 1',3' thiazolo[4',5':17,16] 5alpha androstane , antineoplastic agent , aromatase , epidermal growth factor receptor , ethyl 17beta hydroxyspiro[oxiran 2',3beta androst 4 en] 3' carboxylate , ethyl 3beta hydroxy spiro[oxiran 2',17beta 5alpha androstane] 3 carboxylate , spiro[oxiran 2',17beta 5alpha androstane] , spiro[oxiran 2',3beta 5alpha androstane] , steroid , sulforhodamine B , unclassified drug , unindexed drug , vasculotropin , antineoplastic activity , bioassay , breast cancer , cancer cell , conference paper , controlled study , cytotoxicity , drug potentiation , drug structure , drug synthesis , gene expression , genetic analysis , human , human cell , IC 50 , in vitro study , reverse transcription polymerase chain reaction , structure activity relation , Antineoplastic Agents , Aromatase , Breast Neoplasms , Cell Line, Tumor , Drug Screening Assays, Antitumor , Female , Gene Expression , Gene Expression Profiling , Humans , Inhibitory Concentration 50 , Steroids , Structure-Activity Relationship , Transcription Factor AP-2 , Vascular Endothelial Growth Factor A

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 ?M) exhibited more inhibitory influence on MCF-7 growth than the reference drug doxorubicin (Dox) (IC 50 = 4.5 ?M) 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-2?). Noteworthy, compounds 17, 20 and 22c showed the most pronounced effect in this respect. � 2011 Elsevier Ltd. All rights reserved.