El Newahie A.M.S.Nissan Y.M.Ismail N.S.M.Abou El Ella D.A.Khojah S.M.Abouzid K.A.M.Pharmaceutical Organic Chemistry DepartmentFaculty of PharmacyOctober University for Modern Science and Arts (MSA)Cairo12611Egypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyCairo UniversityCairo11562Egypt; Pharmaceutical Chemistry DepartmentFaculty of PharmacyOctober University for Modern Science and Arts (MSA)Cairo12611Egypt; Pharmaceutical Chemistry DepartmentFaculty of Pharmaceutical Sciences and Pharmaceutical IndustriesFuture University in EgyptCairo12311Egypt; Pharmaceutical Chemistry DepartmentFaculty of Pharmacy Ain Shams UniversityAbbassiaCairo 11566Egypt; Department of Pharmaceutical ChemistryFaculty of PharmacyNahda UniversityBeni Suef62513Egypt; Biochemistry DepartmentFaculty of ScienceKing Abdulaziz UniversityJeddah21589Saudi Arabia; Department of Organic and Medicinal ChemistryFaculty of PharmacyUniversity of Sadat CityMenoufia32897Egypt2020-01-092020-01-09201914203049https://doi.org/10.3390/molecules24061175PubMed ID 30934622https://t.ly/52XNYScopusThe quinoxaline scaffold is a promising platform for the discovery of active chemotherapeutic agents. Three series of quinoxaline derivatives were synthesized and biologically evaluated against three tumor cell lines (HCT116 human colon carcinoma, HepG2, liver hepatocellular carcinoma and MCF-7, human breast adenocarcinoma cell line), in addition to VEGFR-2 enzyme inhibition activity. Compounds VIId, VIIIa, VIIIc, VIIIe and XVa exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound VIIIc induced a significant disruption in the cell cycle profile and cell cycle arrest at the G2/M phase boundary. In further assays, the cytotoxic effect of the highly active compounds was determined using a normal Caucasian fibroblast-like fetal lung cell line (WI-38). Compound VIIIc could be considered as a lead compound that merits further optimization and development as an anti-cancer and an apoptotic inducing candidate against the HCT116 cell line. � 2019 by the authors.EnglishAnti-cancer activityCell cycleQuinoxalineSynthesisantineoplastic agentquinoxaline derivativevasculotropin receptor 2antagonists and inhibitorsapoptosiscell cycle checkpointcell proliferationchemical structurechemistrydose responsedrug designdrug effecthumannuclear magnetic resonance spectroscopystructure activity relationsynthesistumor cell lineAntineoplastic AgentsApoptosisCell Cycle CheckpointsCell Line, TumorCell ProliferationChemistry Techniques, SyntheticDose-Response Relationship, DrugDrug DesignHumansMagnetic Resonance SpectroscopyMolecular StructureQuinoxalinesStructure-Activity RelationshipVascular Endothelial Growth Factor Receptor-2Articlehttps://doi.org/10.3390/molecules24061175PubMed ID 30934622