Abstract
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 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.
Highlights
Cancer is a major human health problem that remains the second highest cause of mortality worldwide [1], where 1,688,780 new cancer cases and 600,920 cancer deaths were projected to occur in the United States in 2017 [2]
Quinoxalines are prepared by the reaction of o-phenylenediamine and α-ketocarboxylic acids [19]
The reactions were monitored the purities of theplates compounds checked by ascending layer chromatography (TLC)
Summary
Cancer is a major human health problem that remains the second highest cause of mortality worldwide [1], where 1,688,780 new cancer cases and 600,920 cancer deaths were projected to occur in the United States in 2017 [2]. Human protein tyrosine kinases (PTKs) play a central role in human carcinogenesis [3], whereas cell cycle progression, cell division and proliferation are viewed as a sequence of events controlled by a cascade of those protein kinases, so PTKs have emerged as promising new cancer therapy targets [4]. In 2016, Zghaib et al reported that imidazo[1,2-a]quinoxaline derivatives were major microtubule-interfering agents with potent anticancer activity [7]. Quinoxalines with amide and sulphonamide moieties have been reported to inhibit the growth of human tumor cell lines [8]. Ghorab et al [9] designed (quinoxalin-2-yl)benzene sulphonamide derivative 1 (Figure 1) with
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