title: Design and synthesis of 21-alkynylaryl pregnenolone derivatives and evaluation of their anticancer activity.
abstract: A series of novel C21-alkynylaryl derivatives of pregnenolone were synthesized and screened for anticancer activity against a panel of seven human cancer cell lines (LNCaP, A549, MCF7, HeLa, A431, HepG2, HT29). The data revealed that these compounds can be potential antitumour agents against the specific cell models. Compound 6f bearing a 2-trifluoromethylphenyl group displayed improved cytotoxicity towards all cancer cell lines used. A431 cells were the most sensitive with derivatives 6e-6h bearing electron withdrawing substituents exhibiting high potency with IC50 values ranging between 2.18 and 0.54μM and drastic inhibition of the prosurvival PI3K-Akt/PKB pathway.
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece.
authors.forename: György
authors.initials: G
authors.lastname: Szalóki
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece.
authors.forename: Athanasia
authors.initials: A
authors.lastname: Pantzou
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece.
authors.forename: Kyriakos C
authors.initials: KC
authors.lastname: Prousis
authors.affiliation: University of Athens, Department of Biology, Division of Animal and Human Physiology, Panepistimiopolis, Athens 15784, Greece.
authors.forename: Olga
authors.initials: O
authors.lastname: Mavrofrydi
authors.affiliation: University of Athens, Department of Biology, Division of Animal and Human Physiology, Panepistimiopolis, Athens 15784, Greece.
authors.forename: Panagiota
authors.initials: P
authors.lastname: Papazafiri
authors.affiliation: Institute of Biology, Medicinal Chemistry and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece. Electronic address: tcalog@eie.gr.
authors.forename: Theodora
authors.initials: T
authors.lastname: Calogeropoulou
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011284:Pregnenolone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011284:Pregnenolone; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt
keywords: Alkynylaryl derivatives; Anticancer activity; Pregnenolone