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Design, synthesis and antitumor activity of novel quinoline-benzimidazolamidine hybrids

Cancer is one of the most prominent health issues responsible for more than 1 million deaths per year in EU, costing annually more than billion euros. One of the emerging strategies for overcoming the drawbacks of the available anticancer therapeutics is the development of hybrid agents, composed of two distinct pharmocophores [1]. In continuing our work on the synthesis and evaluation of hybrid molecules [2] we have synthesized two series of new hybrids in which 7-chloro-4-aminoquinoline is linked with two different linkers to a benzimidazole amidine moiety. Moieties have been chosen, because both of them show anticancer activity. Several 7- chloro-4- aminoquinoline based antimalarial therapeutics are tested for their anticancer activity, two of them (chloroquine and hydroxychloroquine) are currently investigated in clinical trials for cancer therapy [3]. On the other hand benzimidazole moiety is found in many known pharmaceuticals, displaying besides anticancer a variety of biological effects, also positively charged amidine groups are known for their cellular and nuclear uptake. Novel compounds were evaluated for their in vitro cytotoxic activity against normal epithelial (MDCK1), cervix adenocarcinoma (HeLa), colon adenocarcinoma (CaCo2), and leukemia (K562 and RaJi) cell lines using MTT assay.

Quinoline, benzimidazolamidine, hybrids, antitumor activity

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