Design, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugs

dc.authoridYelekci, Kemal/0000-0002-0052-4926
dc.authoridCetin, M. Mustafa/0000-0002-6443-0232
dc.authorwosidUnruh, Daniel/HGD-1250-2022
dc.authorwosidYelekci, Kemal/B-1431-2019
dc.contributor.authorYelekçi, Kemal
dc.contributor.authorPeng, Wenjing
dc.contributor.authorUnruh, Daniel
dc.contributor.authorMayer, Michael F.
dc.contributor.authorMechref, Yehia
dc.contributor.authorYelekci, Kemal
dc.date.accessioned2023-10-19T15:11:46Z
dc.date.available2023-10-19T15:11:46Z
dc.date.issued2022
dc.department-temp[Cetin, M. Mustafa; Yelekci, Kemal] Kadir Has Univ, Fac Engn & Nat Sci, Dept Mol Biol & Genet, Istanbul, Turkey; [Peng, Wenjing; Unruh, Daniel; Mayer, Michael F.; Mechref, Yehia] Texas Tech Univ, Dept Chem & Biochem, Lubbock, TX 79409 USAen_US
dc.description.abstractBreast cancer is the second type of cancer with a high probability of brain metastasis and has always been one of the main problems of breast cancer research due to the lack of effective treatment methods. Demand for developing an effective drug against breast cancer brain metastasis and finding molecular mechanisms that play a role in effective treatment are gradually increasing. However, there is no effective anticancer therapeutic drug or treatment method specific to breast cancer, in particular, for patients with a high risk of brain metastases. It is known that mTOR and HDAC enzymes play essential roles in the development of breast cancer brain metastasis. Therefore, it is vital to develop some new drugs and conduct studies toward the inhibition of these enzymes that might be a possible solution to treat breast cancer brain metastasis. In this study, a series of 1,10-phenanthroline and Prodigiosin derivatives consisting of their copper(I) complexes have been synthesized and characterized. Their biological activities were tested in vitro on six different cell lines (including the normal cell line). To obtain additional parallel validations of the experimental data, some in silico modeling studies were carried out with mTOR and HDAC1 enzymes, which are very crucial drug targets, to discover novel and potent drugs for breast cancer and related brain metastases disease.en_US
dc.description.sponsorshipNational Science Foundation [CHE-0847736]; National Institutes of Health (NIH) [1R01GM112490-08, 1R01GM130091-03]en_US
dc.description.sponsorshipFinancial support from the National Science Foundation (MM research grant CHE-0847736) is gratefully acknowledged. This work was also supported by grants from National Institutes of Health (NIH, 1R01GM112490-08 and 1R01GM130091-03).en_US
dc.identifier.citation0
dc.identifier.doi10.3389/fphar.2022.980479en_US
dc.identifier.issn1663-9812
dc.identifier.pmid36267272en_US
dc.identifier.scopus2-s2.0-85140232268en_US
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.3389/fphar.2022.980479
dc.identifier.urihttps://hdl.handle.net/20.500.12469/5211
dc.identifier.volume13en_US
dc.identifier.wosWOS:000871099800001en_US
dc.identifier.wosqualityQ1
dc.khas20231019-WoSen_US
dc.language.isoenen_US
dc.publisherFrontiers Media Saen_US
dc.relation.ispartofFrontiers in Pharmacologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectSchiff-Base-CopperEn_Us
dc.subjectBreast-Cancer CellsEn_Us
dc.subjectHistone Deacetylase-1En_Us
dc.subjectProteasome InhibitorsEn_Us
dc.subjectMetal-ComplexesEn_Us
dc.subjectExpressionEn_Us
dc.subjectApoptosisEn_Us
dc.subjectRingEn_Us
dc.subjectInductionEn_Us
dc.subjectPrognosisEn_Us
dc.subjectSchiff-Base-Copper
dc.subjectBreast-Cancer Cells
dc.subjectHistone Deacetylase-1
dc.subjectbreast cancer brain metastasesen_US
dc.subjectProteasome Inhibitors
dc.subject1,10-phenanthrolineen_US
dc.subjectMetal-Complexes
dc.subjectanticancer therapeutic drugsen_US
dc.subjectExpression
dc.subjectmTORen_US
dc.subjectApoptosis
dc.subjectHDACen_US
dc.subjectRing
dc.subjectHDAC1en_US
dc.subjectInduction
dc.subjectmolecular modelingen_US
dc.subjectPrognosis
dc.subjectprodigiosinen_US
dc.titleDesign, synthesis, molecular modeling, and bioactivity evaluation of 1,10-phenanthroline and prodigiosin (Ps) derivatives and their Copper(I) complexes against mTOR and HDAC enzymes as highly potent and effective new anticancer therapeutic drugsen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

Files

Original bundle

Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
5211.pdf
Size:
2.51 MB
Format:
Adobe Portable Document Format
Description:
Tam Metin / Full Text