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dc.contributor.authorŞahin, Zafer
dc.contributor.authorBiltekin, Sevde Nur
dc.contributor.authorYurttaş, Leyla
dc.contributor.authorBerk, Barkın
dc.contributor.authorÖzhan, Yağmur
dc.contributor.authorSipahi, Hande
dc.contributor.authorGao, Zhanguo
dc.contributor.authorJacobson, Kenneth A.
dc.contributor.authorDemirayak, Şeref
dc.date.accessioned2021-01-15T08:40:34Z
dc.date.available2021-01-15T08:40:34Z
dc.date.issued2021en_US
dc.identifier.citationŞahin, Z., Biltekin, S. N., Yurttaş, L., Berk, B., Özhan, Y., Sipahi, H. ... Demirayak, Ş. (2021). Novel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: Adenosine receptor binding and potent PDE4 inhibition. European Journal of Medicinal Chemistry, 212. https://dx.doi.org/10.1016/j.ejmech.2020.113125en_US
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.urihttps://dx.doi.org/10.1016/j.ejmech.2020.113125
dc.identifier.urihttps://hdl.handle.net/20.500.12511/6258
dc.description.abstractThiouracil and thiocytosine are important heterocyclic pharmacophores having pharmacological diversity. Antitumor and antiviral activity is commonly associated with thiouracil and thiocytosine derivatives, which are well known fragments for adenosine receptor affinity with many associated pharmacological properties. In this respect, 33 novel compounds have been synthesized in two groups: 24 thiouracil derivatives (4a-x) and 9 thiocytosine derivatives (5a-i). Antitumor activity of all the compounds was determined in the U87 MG glioblastoma cell line. Compound 5e showed an anti-proliferative IC50 of 1.56 μM, which is slightly higher activity than cisplatin (1.67 μM). The 11 most active compounds showed no signficant binding to adenosine A1, A2A or A2B receptors at 1 μM. Brain tumors express high amounts of phosphodiesterases. Compounds were tested for PDE4 inhibition, and 5e and 5f showed the best potency (5e: 3.42 μM; 5f: 0.97 μM). Remakably, those compounds were also the most active against U87MG. However, the compounds lacked a cytotoxic effect on the HEK293 healthy cell line, which encourages further investigation.en_US
dc.description.sponsorshipNational Institute of Diabetes and Digestive and Kidney Diseasesen_US
dc.description.sponsorshipUnited States Department of Health & Human Services National Institutes of Health (NIH) - USAen_US
dc.language.isoengen_US
dc.publisherElsevier France-Editions Scientifiques Medicales Elsevieren_US
dc.rightsinfo:eu-repo/semantics/embargoedAccessen_US
dc.subjectThiouracilen_US
dc.subjectThiocytosineen_US
dc.subjectAdenosineen_US
dc.subjectU87en_US
dc.subjectAntitumoren_US
dc.subjectPhosphosdiesteraseen_US
dc.subjectPDEen_US
dc.subjectHEK293en_US
dc.subjectMCF7en_US
dc.titleNovel cyanothiouracil and cyanothiocytosine derivatives as concentration-dependent selective inhibitors of U87MG glioblastomas: Adenosine receptor binding and potent PDE4 inhibitionen_US
dc.typearticleen_US
dc.relation.journalEuropean Journal of Medicinal Chemistryen_US
dc.departmentİstanbul Medipol Üniversitesi, Eczacılık Fakültesi, Eczacılık Meslek Bilimleri Bölümü, Farmasötik Kimya Ana Bilim Dalıen_US
dc.authorid0000-0002-5976-676Xen_US
dc.authorid0000-0003-1896-2729en_US
dc.authorid0000-0001-6047-2796en_US
dc.authorid0000-0002-0841-1299en_US
dc.identifier.volume212en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.1016/j.ejmech.2020.113125en_US


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