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2022-07-31Zeitschriftenartikel DOI: 10.3390/molecules27154898
Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study
dc.contributor.authorSalem, Manar G.
dc.contributor.authorEl-Maaty, Dina M. Abu
dc.contributor.authorEl-Deen, Yassmina I. Mohey
dc.contributor.authorElesawy, Basem H.
dc.contributor.authorAskary, Ahmad El
dc.contributor.authorSaleh, Asmaa
dc.contributor.authorSaied, Essa M.
dc.contributor.authorEl Behery, Mohammed
dc.date.accessioned2022-08-11T11:45:26Z
dc.date.available2022-08-11T11:45:26Z
dc.date.issued2022-07-31none
dc.date.updated2022-08-03T15:58:15Z
dc.identifier.urihttp://edoc.hu-berlin.de/18452/25811
dc.description.abstractBreast cancer is the most common cancer in women, responsible for over half a million deaths in 2020. Almost 75% of FDA-approved drugs are mainly nitrogen- and sulfur-containing heterocyclic compounds, implying the importance of such compounds in drug discovery. Among heterocycles, thiazole-based heterocyclic compounds have demonstrated a broad range of pharmacological activities. In the present study, a novel set of 1,3-thiazole derivatives was designed and synthesized based on the coupling of acetophenone derivatives, and phenacyl bromide was substituted as a key reaction step. The activity of synthesized compounds was screened against the proliferation of two breast cancer cell lines (MCF-7 and MDA-MB-231). Almost all compounds exhibited a considerable antiproliferative activity toward the breast cancer cells as compared to staurosporine, with no significant cytotoxicity toward the epithelial cells. Among the synthesized compounds, compound 4 exhibited the most potent antiproliferative activity, with an IC50 of 5.73 and 12.15 µM toward MCF-7 and MDA-MB-231 cells, respectively, compared to staurosporine (IC50 = 6.77 and 7.03 µM, respectively). Exploring the mechanistic insights responsible for the antiproliferative activity of compound 4 revealed that compound 4 possesses a significant inhibitory activity toward the vascular endothelial growth factor receptor-2 (VEGFR-2) with (IC50 = 0.093 µM) compared to Sorafenib (IC50 = 0.059 µM). Further, compound 4 showed the ability to induce programmed cell death by triggering apoptosis and necrosis in MCF-7 cells and to induce cell cycle arrest on MCF-7 cells at the G1 stage while decreasing the cellular population in the G2/M phase. Finally, detailed in silico molecular docking studies affirmed that this class of compounds possesses a considerable binding affinity toward VEGFR2 proteins. Overall, these results indicate that compound 4 could be a promising lead compound for developing potent anti-breast cancer compounds.eng
dc.description.sponsorshipFaculty of Pharmacy, Suez Canal University, and Faculty of Science, Port Said University, Egypt
dc.description.sponsorshipPrincess Nourah bint Abdulrahman University Researchers Supporting
dc.description.sponsorshipTaif University Researchers
dc.language.isoengnone
dc.publisherHumboldt-Universität zu Berlin
dc.rights(CC BY 4.0) Attribution 4.0 Internationalger
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subject1,3-thiazoleeng
dc.subject2-hydrazinyl-1,3-thiazoleeng
dc.subjectbreast cancereng
dc.subjectanticancer activityeng
dc.subjectantiproliferationeng
dc.subjectVEGFR-2 kinase activityeng
dc.subjectapoptosiseng
dc.subjectcell cycle arresteng
dc.subjectmolecular dockingeng
dc.subject.ddc540 Chemie und zugeordnete Wissenschaftennone
dc.titleNovel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Studynone
dc.typearticle
dc.identifier.urnurn:nbn:de:kobv:11-110-18452/25811-4
dc.identifier.doi10.3390/molecules27154898none
dc.identifier.doihttp://dx.doi.org/10.18452/25125
dc.type.versionpublishedVersionnone
local.edoc.container-titleMoleculesnone
local.edoc.pages26none
local.edoc.type-nameZeitschriftenartikel
local.edoc.institutionMathematisch-Naturwissenschaftliche Fakultätnone
local.edoc.container-typeperiodical
local.edoc.container-type-nameZeitschrift
local.edoc.container-publisher-nameMDPInone
local.edoc.container-publisher-placeBaselnone
local.edoc.container-volume27none
local.edoc.container-issue15none
local.edoc.container-articlenumber4898none
dc.identifier.eissn1420-3049

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