Design and Synthesis of New Quinoxaline Derivatives as Anticancer Agents and Apoptotic Inducers

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 6; p. 1175
• Main Authors: El Newahie, Aliya M S, Nissan, Yassin M, Ismail, Nasser S M, Abou El Ella, Dalal A, Khojah, Sohair M, Abouzid, Khaled A M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-03-2019; MDPI
• Subjects: Adenocarcinoma; anti-cancer activity; Apoptosis; Breast; Cancer; Cell cycle; Cell division; Chemotherapy; Chloride; Colon; Cytotoxicity; Design; Epidermal growth factor; Fetuses; Hepatocellular carcinoma; Hydrochloric acid; Kinases; Lead compounds; Optimization; Proteins; Quinoxaline; Quinoxalines; synthesis; Tumor cell lines; Vascular endothelial growth factor receptors; synthesis; anti-cancer activity; quinoxaline; cell cycle
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24061175

The 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
,
,
,
and
exhibited promising activity against the tested cell lines and weak activity against VEGFR-2. Compound
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
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.