Synergistic fusion of carbazole, quinoline, and chalcone scaffolds: A computational and experimental exploration of hybrid compounds as selective anticancer agents

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dc.authoridsalima, tabti/0000-0003-0116-8350;
dc.contributor.authorMusatat, Ahmad Badreddin
dc.contributor.authorKiliccioglu, Ilker
dc.contributor.authorLouaileche, Tinhinane
dc.contributor.authorDulger, Gorkem
dc.contributor.authorMaouche, Chaima
dc.contributor.authorTabti, Salima
dc.contributor.authorKurman, Yener
dc.date.accessioned2025-10-11T20:48:29Z
dc.date.available2025-10-11T20:48:29Z
dc.date.issued2025
dc.departmentDüzce Üniversitesien_US
dc.description.abstractNovel carbazole-quinoline-chalcone hybrids (nQCC1-4) were synthesized via Claisen-Schmidt condensation and evaluated against AGS gastric adenocarcinoma cells. The most potent compound, 1QCC-1, exhibited significant antiproliferative activity (IC50 values of 19.11 mu g/mL and 7.91 mu g/mL at 24 h and 48 h). Compounds 1QCC-4, 1QCC-3, and 2QCC-2 demonstrated comparable cytotoxic efficacy against AGS cells. Density functional theory (DFT) calculations revealed substituent-dependent electronic properties, with chloro-quinoline derivatives displaying enhanced electrophilicity (omega = 13.745-14.157 eV) and reduced HOMO-LUMO gaps (Delta E = 3.304-3.347 eV), correlating with improved bioactivity profiles. Molecular docking studies identified robust binding interactions with oncogenic targets, MAPK1 p38 kinase, HER2, and RhoA, with 1QCC-4 exhibiting superior binding affinity for HER2 (Delta G = -12.05 kcal/mol, IC50 = 1.48 nM) through hydrogen bonding with Lys114 and it-alkyl interactions with Leu156. ADMET profiling highlighted favorable drug-likeness parameters despite solubility challenges (LogS = -7.846 to -6.291) and potential CYP450 inhibition. Non-covalent interaction (NCI-RDG) and molecular electrostatic potential (MEP) analyses elucidated key stabilizing interactions and nucleophilic/electrophilic hotspots. These hybrids represent a strategic integration of natural product pharmacophores, leveraging synergistic electronic and steric effects for selective kinase inhibition, positioning them as promising leads for targeted gastric cancer therapy.en_US
dc.description.sponsorshipDuzce University Scientific Research Projects Unit [2025.05.03.1579]en_US
dc.description.sponsorshipThis study was financially supported by Duzce University Scientific Research Projects Unit (Project number: 2025.05.03.1579) .en_US
dc.identifier.doi10.1016/j.molstruc.2025.143401
dc.identifier.issn0022-2860
dc.identifier.issn1872-8014
dc.identifier.scopus2-s2.0-105011257477en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1016/j.molstruc.2025.143401
dc.identifier.urihttps://hdl.handle.net/20.500.12684/21947
dc.identifier.volume1348en_US
dc.identifier.wosWOS:001552072000001en_US
dc.identifier.wosqualityQ2en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofJournal of Molecular Structureen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.snmzKA_WOS_20250911
dc.subjectCarbazoleen_US
dc.subjectChalconeen_US
dc.subjectQuinolineen_US
dc.subjectAGS Canceren_US
dc.subjectIn silicoen_US
dc.titleSynergistic fusion of carbazole, quinoline, and chalcone scaffolds: A computational and experimental exploration of hybrid compounds as selective anticancer agentsen_US
dc.typeArticleen_US

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