Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones.

Graphical abstract Highlights • Indole hydrazones were designed and easy synthesized. • Synthesized compounds were assayed in vitro as antioxidants and photoprotective agents. • Synthesized compounds were assayed in vitro for their antiproliferative activity on human melanoma and leukemia cells. • The hydrazones 16 and 17 showed antioxidant activity in DPPH, FRAP and ORAC test as well as photoprotective effect. • The hydrazones 11 , 16 and 17 inhibited the growth of Colo-38 and K-562 cells with sub-micromolar IC 50 values. Abstract Two series of indole derivatives 4 – 17, 20 – 22 were easily prepared and assayed for their radical-scavenging ability. Arylidene-1H-indole-2-carbohydrazones showed different extent antioxidant activity in DPPH, FRAP and ORAC assays. Good antioxidant activity is related to the number and position of hydroxyl groups on the arylidene moiety as well as to the presence of methoxy or 4-(diethylamino) group. On the contrary low antioxidant activity is showed by the isomeric 1H-indol-2-yl(methylene)-benzohydrazides. Furthermore, hydrazones 4 – 17 showed photoprotective capacities with satisfactory in vitro SPF as compared to the commercial PBSA sunscreen filter. The indole 16 and 17 , showing the best antioxidant and photoprotective profile, were included in different formulation and their topical release was evaluated. Varying the formulation composition, it was possible to optimize skin adsorption and solubility of the active indole in the formulation. The antiproliferative effect of the hydrazones 4 – 17 was tested on human erythroleukemia K562 and melanoma Colo-38 cells. Hydrazones 11 , 16 and 17 showed growth inhibition at sub micromolar concentrations on both cell lines. These results indicate indole hydrazones as potential multifunctional molecules especially in the treatment of neoplastic diseases being the good antioxidant properties of 16 and 17 correlated to their high antiproliferative activity. [ABSTRACT FROM AUTHOR]