Can Functionalization of Quinoline Derivatives Be Exploited to Control Quinolines Cytotoxic Effects?

Quinoline and its variety of derivatives have long been studied for their biological activities such as anticancer, antitumor, anti-inflammatory, and antioxidant properties.
As part of our research, we are interested in the synthesis and development of heterocyclic compounds such as quinoline derivatives and poly-pyridyl materials that might have potential biological activities. Particularly, anti-cancerous and anti-bacterial properties of such compounds are of our interest.
A previously synthesized mixture of two quinoline derivative isomers (7-methylquinoline and 5-methylquinoline (A B)) and other four quinoline derivatives (7-methyl-8-nitro-quinoline (C), 7- (β-trans- (N,N-dimethylamino) ethenyl) -8-nitroquinoline (D), 8-nitro-7-quinolinecarbaldehyde (E), and 8-Amino-7-quinolinecarbaldehyde (F)) were selected to evaluate their in vitro cytotoxicity against human epithelial colorectal carcinoma (Caco-2) cultured cells by MTT assay. The IC50 values for the mixture and other compounds were calculated by SigmaPlot 12.0 software.
Compounds (A B), (C), (D), (E), and (F) showed IC50 values of 2.62, 1.87, 0.93, 0.53, and 1.140 µM, respectively.
Our investigation suggested that all compounds were cytotoxic against Caco-2 cell lines. We observed that the previously synthesized quinoline derivatives (A B), (C), (D), (E), and (F) in a reaction sequence show an influence in cytotoxicity against Caco-2 cell lines. Based on our evaluation, quinoline derivative (E) showed the highest cytotoxicity against the cultured cells compared to the other compounds we studied. An increase in cytotoxicity was observed from the mixture (A B) to the compounds (C), (D) and (E), in sequence, while cytotoxicity of compound (F) appeared to be less than that of compound (E). Based on our observations, we concluded that functionalization of the quinoline derivatives we studied resulted in a change in cytotoxic activities of the compounds. Therefore, the functionalization strategy we employed for the quinoline derivatives could be useful in controlling the cytotoxic level of such compounds.