Synthesis of 1,2,3-Triazole Benzophenone Derivatives and Evaluation of in vitro Sun Protection, Antioxidant Properties, and Antiproliferative Activity on HT-144 Melanoma Cells

Benzophenones display several biological activities, including antioxidant, anticancer, and photoprotective. Furthermore, antioxidants can minimize both ultraviolet absorption and tumor development. In the present investigation, a series of twenty-six 1,2,3-triazole-benzophenone derivatives were synthesized and had their antioxidant, anticancer, and photoprotective effects evaluated. For the compounds synthesis, 4,4’-dihydroxybenzophenone (1a) and 2,4-dihydroxybenzophenone (1b) were propargylated, affording the alkynes bis(4-(prop-2-yn-1-yloxy))benzophenone (2a) and (2-hydroxy-4-(prop-2-yn-1-yloxy))benzophenone (2b), respectively. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between the compounds 2a/2b and several benzyl azides gave the 1,2,3-triazole-benzophenone derivatives with yields ranging from 35 to 95%. The 1,2,3-triazole-benzophenone derivatives at the concentration of 0.2 μg mL^-1 (a no-cytotoxic concentration) exhibited a solar protection factor (SPF) comparable to positive control benzophonen-3 (BP-3). Concerning their antioxidant and cytotoxic effects, the derivatives from 1b showed high in vitro antioxidant effects as well as cytotoxicity against A549 (lung carcinoma), MCF-7 (breast carcinoma), and HT-144 (metastatic melanoma) cell lines, without significant cytotoxicity to a non-cancerous cell line. Derivatives 19, 20, and 24 induced cell death and cell cycle arrest at G1/S in HT-144 melanoma cells.

Keywords:
benzophenone; 1,2,3-triazole; CuAAC reaction; antioxidant; photoprotective; cytotoxicity