In-Vitro Evaluation of Antioxidant, Antiproliferative and Photo-Protective Activities of Benzimidazolehydrazone Derivatives

Abstract

In the search of multifunctional compounds we designed benzimidazole derivatives endowed with phenolic hydroxy groups and a hydrazone moiety as potential radical-scavenger and the antioxidant agents. The target molecules have been prepared by a simple synthetic procedure and tested for their antioxidant activity by DPPH, FRAP, and ORAC test, for photoprotective activity against UV rays and for antiproliferative activity against Colo-38 melanoma cells. Furthermore, two different dermocosmetic formulations were prepared with the compounds endowed with the best antioxidant and photoprotective profile and their release from formulation evaluated using Franz Cells system. High antioxidant activity is related to the presence of at least two hydroxy groups on arylidene moiety of benzimidazoles. Structure activity analysis revealed that the position of hydroxy groups is crucial for antioxidant activity as well as the presence of a 2-hydroxy-4-(diethylamino)arylidene group. The same correlation pattern was found to be related to photoprotective activity resulting in an UVA Protection Factor better than the commercial solar filter PBSA and antiproliferative activity against melanoma cells without producing cytotoxicity on normal keratinocytes. The release analysis indicated that high antioxidant activities are achieved with limited release at concentration compatible with the use as UV sunscreen filter.

Synthesis and evaluation of antioxidant and antiproliferative activity of 2-arylbenzimidazoles

“…The activity of the synthesized derivatives against DPPH • radical was tested following the Wang et al method [25] modified as previously reported [17]. The results are expressed as μmol TE/g corresponding to an inhibition of the radical equal to 50%, except for some compounds.…”

“…Cell growth inhibition assays were carried out using two human cell lines, melanoma Colo38 [30,31,17] and keratinocyte HaCat [31,32], cells. Colo 38 cell line was maintained in RPMI 1640, supplemented with 10% fetal bovine serum (FBS), penicillin (100 Units mL-1), streptomycin (100 μg mL-1) and glutamine (2 mM) (complete medium); the pH of the medium was 7.2 and the incubation was performed at 37 °C in a 5% CO 2 atmosphere.…”

“…The final product, called Oxisol (2-(3,4-dihydroxy-phenyl)-1H-benzimidazole-5-carboxylic acid), is not only a powerful antioxidant and absorbs in the UVA range, but is also equipped with SPF booster effect [15][16]. As a continuation of our efforts to identify dualistic molecules [17,18] able to act, at the same time, as antioxidant and photoprotective agents here we describe the design, synthesis and biological evaluation of three series of benzimidazoles differing for the substituent at 5-position and bearing a variety of hydroxyaryl moieties at 2-position.…”

New 1H-benzimidazole-2-yl hydrazones with combined antiparasitic and antioxidant activity

“…1). [15][16][17] On the other hand, in our previous paper, 18 we reported the synthesis of a series of benzimidazolyl-2-hydrazones of uoro-, hydroxy-and methoxy-substituted benzaldehydes and 1,3benzodioxole-5-carbaldehyde (Fig. 1).…”

Organofluorine Hydrazone Derivatives as Multifunctional Anti‐Alzheimer's Agents with CK2 Inhibitory and Antioxidant Features

“…Hydrazones, as largely nontoxic entities, have attracted significant attention in drug development. They are considered as part of hybrid compounds when designing more effective, often multitarget therapeutics [23–26] . Hydrazones exhibit a broad spectrum of biological activities and have been described in the treatment of tuberculosis, [27] malaria [28] or as antiviral [29,30] and anticancer agents [31] .…”