Synthesis of novel cyanine dyes as antitumor agents

• Published in: Archiv der Pharmazie (Weinheim) 2021-03, Vol.354 (3), p.e2000186-n/a
• Main Authors: Fadda, Ahmed A., Tawfik, Eman H., Abdel‐Motaal, Marwa, Selim, Yasser A.
• Format: Article
• Language: English
• Subjects: 2,6‐dimethyl pyridine; 2‐benzylpyridine; Breast cancer; Cytotoxicity; Dyes; monomethine cyanine dye; Pharmacology; pyridinium salts cytotoxic activity; α‐tetralone
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.202000186

In this study, some novel cyanine dyes, 1, 3, and 5−15, were synthesized by a one‐pot step reaction of pyridinium salts 2 and/or 4 with benzenaminium salt 1. N‐{[1‐Chloro‐3,4‐dihydronaphthalen‐2‐yl)methylene]benzenaminium} chloride 1 was obtained by the reaction of α‐tetralone with Vilsmeier−Haack reagent, followed by a mixture of an equimolar ratio of anilin/ethanol (1:1). All new cyanine dyes were evaluated in vitro for their anticancer activity against two cell lines, that is, HepG2 (human hepatocellular liver carcinoma) and MCF‐7 (breast cancer). The obtained results were compared with human lung fibroblasts (WI‐38) and Vero cells (derived from the kidney of an African green monkey) as normal cells. In particular, some of these compounds, 6, 9, 13, and 14, were found to be the most potent derivatives against all the cancer cell lines, without effect on the normal cells. According to the structure–activity relationship, compound 13 (IC50 = 8.8 µg/ml) exhibited a higher activity against HepG2 cells, as it contains the azo group and two phenyl rings and due to the presence of the π‐conjugated system attached to the two pyridine rings. Compound 6 (IC50 = 8 µg/ml) exhibited a higher activity against MCF‐7 cells, as it contains two chlorine atoms and the π‐conjugated system of the pyridine rings. New cyanine dyes were produced by a novel one‐pot step reaction between pyridinium salts and/or benzenaminium salt, using the Vilsmeier−Haack reagent. The new cyanine dyes were tested for their in vitro cytotoxicity against human hepatocellular liver carcinoma cells (HepG2), breast cancer cells (MCF‐7), and normal cells (WI‐38, Vero). Some of these compounds showed good and moderate activities, compared with the commercially available 5‐fluorouracil as a positive control.