In vitro cytotoxicity, gene expression, bioinformatics, biochemical analysis, and in silico analysis of synthesized carbonitrile derivatives

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dc.authoridTUZUN, BURAK/0000-0002-0420-2043
dc.contributor.authorTuzun, Burak
dc.contributor.authorAgbektas, Tugba
dc.contributor.authorNaghiyev, Farid N.
dc.contributor.authorTas, Ayca
dc.contributor.authorZontul, Cemile
dc.contributor.authorOzum, Unal
dc.contributor.authorKhalilov, Ali N.
dc.date.accessioned2025-05-04T16:47:26Z
dc.date.available2025-05-04T16:47:26Z
dc.date.issued2025
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractIn this work, an efficient single-step green synthesis protocol of 2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitriles was applied with the purpose of their biological activity studies. It was found that the cytotoxic activities of 2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitriles in the SHSY-5Y cancer cell line were most active after 72 h of incubation. It was determined that 1,6-diamino-4a-methyl-3-oxo-2,8-diphenyl-2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitrile showed higher anticancer activity on SHSY-5Y cancer cells compared to other molecules. The expression levels of Myc-N, Casp2, Tp53, RAD51, BRCA2, MDM2, BAX and NF-kappa B1 genes were analyzed by RT-PCR method by applying 2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitriles to the SHSY-5Y neuroblastoma cancer cell line. It was observed that there were differences in expression levels between study groups and all differences were found to be statistically significant (p < 0.000). Bioinformatics analysis was performed using the STRING v 11 Protein interaction tool. When the molecules in the SHSY-5Y cell line were compared to the control group, an 80% increase in GSH levels was observed in 1,6-diamino-4a-methyl-3-oxo-2,8-diphenyl-2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitrile and 1,6-diamino-8-(4-chlorophenyl)-4a-methyl-3-oxo-2-phenyl-2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitrile groups. SOD enzyme activity increased significantly in the former group compared to the control and other groups. LDH activity was detected at a higher rate in this cell line compared to the control group. Calculations were made for 2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitriles using the Gaussian software package on B3LYP, HF, and M06-2 x levels with the 6-31++g(d,p) basis sets. The activities of the 2,3,4,4a-tetrahydroisoquinoline-5,7-dicarbonitriles found in the study against SH-SY5Y protein (2F37, 3PBL and 5WIV), comparison has been made. MM/GBSA methods are calculated binding free energy for all molecule and 3PBL protein. Afterwards, ADME/T analysis was performed to examine the effects of the molecules on human metabolism.
dc.description.sponsorshipSivas Cumhuriyet niversitesi [RGD-020]; Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP) [BSU50/50]; Baku State University
dc.description.sponsorshipThe numerical calculations reported in this paper were fully/partially performed at TUBITAK ULAKBIM, High Performance and Grid Computing Center (TRUBA resources). This work was supported by the Scientific Research Project Fund of Sivas Cumhuriyet University (CUBAP) under the project number RGD-020 and Baku State University under the project number BSU50/50.
dc.identifier.doi10.1007/s00706-025-03315-7
dc.identifier.issn0026-9247
dc.identifier.issn1434-4475
dc.identifier.scopus2-s2.0-105002788968
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1007/s00706-025-03315-7
dc.identifier.urihttps://hdl.handle.net/20.500.12418/35621
dc.identifier.wosWOS:001470038000001
dc.identifier.wosqualityQ3
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherSpringer Wien
dc.relation.ispartofMonatshefte Fur Chemie
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250504
dc.subjectNeuroblastoma cancer
dc.subjectGene expression
dc.subjectBioinformatics analysis
dc.subjectMolecular docking
dc.subjectADME/T
dc.titleIn vitro cytotoxicity, gene expression, bioinformatics, biochemical analysis, and in silico analysis of synthesized carbonitrile derivatives
dc.typeArticle

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