SYNTHESIS AND EVALUATION OF THE PHOTOPROTECTIVE, CYTOTOXIC AND ANTIVIRAL ACTIVITY OF BENZOPHENONE DERIVATIVES CONTAINING 1,2,3-TRIAZOLIC PORTIONS

The benzophenones are synthetic and natural compounds presenting a variety of activities, including photoprotective, cytotoxic and antiviral. It is herein described the preparation of a series of twenty-seven benzophenone derivatives bearing 1,2,3-triazole functionalities and the evaluation of their photoprotective, cytotoxic and antiviral on Zika Virus (ZIKV) activities. The compounds were prepared in three steps, namely reduction of benzophenone, alkylation of diphenylmethanol and CuAAC reactions. The in vitro evaluation of the photoprotective activity revealed that the most active derivative 4-((benzhydryloxy)methyl)-1-(4-nitrobenzyl)-1H-1,2,3-triazole (4k) displayed UVB sun protection factor equal to 6,9±0,53, which make this compound a possible candidate to be used in formulations for photoprotective applications. In terms of cytotoxicity, the compounds were evaluated against MDA-MB-231 and B16F10 cell lines. It was observed that the compounds were more active against MDA-MB-231 cells and three of them were capable of reducing cell viability by approximately 55% at 100 µmol L-1. In the antiviral screening against ZIKV, compound 4-(3-benzhydryloxy)propyl)-1-(3-methylbenzyl)-1H-1,2,3-triazole (5j) was the most effective in mantaining Vero cell viability.

二苯甲酮类化合物是一类兼具多种生物活性的合成与天然产物，其活性涵盖光防护、细胞毒性与抗病毒活性。本研究报道了27种含1,2,3-三唑官能团的二苯甲酮衍生物的制备方法，并对其光防护、细胞毒性及抗寨卡病毒（Zika Virus, ZIKV）活性进行了评价。该类化合物通过三步反应制备得到，分别为二苯甲酮的还原、二苯甲醇的烷基化以及CuAAC反应。体外光防护活性评价结果显示，活性最优的衍生物4-((二苯甲氧基)甲基)-1-(4-硝基苄基)-1H-1,2,3-三唑（4k）的UVB防晒因子为6.9±0.53，表明该化合物有望成为光防护类制剂的候选成分。细胞毒性评价针对MDA-MB-231与B16F10两种细胞系展开，结果表明受试化合物对MDA-MB-231细胞的抑制活性更强，其中3种化合物在100 µmol·L⁻¹浓度下可使细胞存活率降低约55%。在抗ZIKV的筛选实验中，化合物4-(3-二苯甲氧基丙基)-1-(3-甲基苄基)-1H-1,2,3-三唑（5j）在维持Vero细胞存活率方面表现最优。