Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives

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dc.authorid0000-0001-6047-2796
dc.authorid0000-0002-2289-7950
dc.authorid0000-0001-6047-2796
dc.authorid0000-0003-1896-2729
dc.authorid0000-0002-0841-1299
dc.contributor.authorŞahin, Zafer
dc.contributor.authorErtaş, Merve
dc.contributor.authorBerk, Barkın
dc.contributor.authorBiltekin, Sevde Nur
dc.contributor.authorYurttaş, Leyla
dc.contributor.authorDemirayak, Şeref
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:50:36Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:50:36Z
dc.date.issued2018
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Temel Eczacılık Bilimleri Bölümü, Farmasötik Mikrobiyoloji Ana Bilim Dalı
dc.descriptionWOS: 000429533300056
dc.descriptionPubMed ID: 29525337
dc.description.abstractSteroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl) thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl) thiazole) were found potent inhibitor of enzyme (IC50: 0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [SBAG-115S168]en_US
dc.description.sponsorshipThe authors acknowledge The Scientific and Technological Research Council of Turkey TUBITAK) for their financial support for the project SBAG-115S168.en_US
dc.identifier.citationŞahin, Z., Ertaş, M., Berk, B., Biltekin, S., Yurttaş, L. ve Demirayak, Ş. (2018). Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives. Bioorganic & Medicinal Chemistry, 26(8), 1986-1995. https://dx.doi.org/10.1016/j.bmc.2018.02.048
dc.identifier.doi10.1016/j.bmc.2018.02.048
dc.identifier.endpage1995
dc.identifier.issn0968-0896
dc.identifier.issn1464-3391
dc.identifier.issue8
dc.identifier.scopusqualityQ1
dc.identifier.startpage1986
dc.identifier.urihttps://dx.doi.org/10.1016/j.bmc.2018.02.048
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2030
dc.identifier.volume26
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ecinfo:eu-repo/grantAgreement/TUBITAK/SOBAG/SBAG-115S168
dc.relation.ispartofBioorganic & Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectAnticancer
dc.subjectMolecular Modelling
dc.subjectThiazoles
dc.subjectAromatase
dc.subjectNon-Steroidal
dc.titleStudies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives
dc.typeArticle

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