Elmegeed G.A.Khalil W.K.B.Mohareb R.M.Ahmed H.H.Abd-Elhalim M.M.Elsayed G.H.Hormones DepartmentNational Research Centre12622 DokkiGizaEgypt; Cell Biology DepartmentNational Research CentreDokkiGizaEgypt; Organic Chemistry DepartmentFaculty of PharmacyOctober University of Modern Sciences and Arts (MSA)October CityEgypt; Chemistry DepartmentFaculty of ScienceCairo UniversityCarioEgypt2020-01-252020-01-2520119680896https://doi.org/10.1016/j.bmc.2011.09.033PubMed ID 22000946https://t.ly/lW7JLScopusAnti-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.EnglishBreast cancerCytotoxicityGene expressionHeterocyclesSteroids17 [4'(1h) oxo 3' phenyl 2' thioxoquinazolin 1 yl]androst 4 en 3 one17 chloroandrost 4 en 3 one2 (3beta acetoxy 5alpha androstan 17 ylideneamino) 4 (methylthio)butanoic acid2 (3beta acetoxy 5alpha androstan 17 ylideneamino) 4 (methythio)butanoic acid2' (3 oxoandrost 4 en 17 yl amino) 5' fluorobenzoic acid2' (3 oxoandrost 4 en 17 yl amino)benzoic acid3' acetylspiro[oxiran 2',17beta 5alpha androstan] 3beta ol3' acetylspiro[oxiran 2',3beta andros 4 en] 17beta ol3' benzoyl spiro[oxiran 2',17beta 5 alpha androstan] 3beta ol3' benzoylspiro[oxiran 2',3beta andros 4 en] 17beta ol3' benzoylspiro[oxiran 2',3beta androst 4 en] 17beta ol3beta acetoxy 1',3' thiazolo[4',5',:17,16] 5alpha androstan 2' acetonitrile3beta acetoxy 16 bromo 5alpha androstan 17 one3beta acetoxy 17 ylideneamino(1',4',5',6' tetrahydro 3' hydroxypyridazin 4' yl) 5alpha androstane3beta acetoxy 17 ylideneamino(n 2' pyrimidylbenzenesulfonamide) 5alpha androstane3beta acetoxy 17 ylideneamino(n 2' pyrimidylbenzenesulfonamidesodium) 5alpha androstane3beta acetoxy 17 ylideneamino[2' (n 2inch pyrimidylbenzenesulfonamide)ethanol] 5alpha androstane3beta acetoxy 2' amino 1',3' thiazolo[4',5':17,16] 5alpha androstane3beta acetoxy n (diethylenetriamine)copper(II)dinitrite 1',3' thiazolo[4',5':17,16] 5alpha androstaneantineoplastic agentaromataseepidermal growth factor receptorethyl 17beta hydroxyspiro[oxiran 2',3beta androst 4 en] 3' carboxylateethyl 3beta hydroxy spiro[oxiran 2',17beta 5alpha androstane] 3 carboxylatespiro[oxiran 2',17beta 5alpha androstane]spiro[oxiran 2',3beta 5alpha androstane]steroidsulforhodamine Bunclassified drugunindexed drugvasculotropinantineoplastic activitybioassaybreast cancercancer cellconference papercontrolled studycytotoxicitydrug potentiationdrug structuredrug synthesisgene expressiongenetic analysishumanhuman cellIC 50in vitro studyreverse transcription polymerase chain reactionstructure activity relationAntineoplastic AgentsAromataseBreast NeoplasmsCell Line, TumorDrug Screening Assays, AntitumorFemaleGene ExpressionGene Expression ProfilingHumansInhibitory Concentration 50SteroidsStructure-Activity RelationshipTranscription Factor AP-2Vascular Endothelial Growth Factor AConference Paperhttps://doi.org/10.1016/j.bmc.2011.09.033PubMed ID 22000946