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In the search for scaffolds for multifunctional compounds we investigated the structure activity relationship of a class of benzimidazole derivatives bearing 5-membered ring. The newly synthesized and the already known compounds were divided into three classes that present different substituent at 5 position of the benzimidazole ring (-H, -COOH or -SO 3 H) and different heterocycle at position 2 (thiophene, furan or pyrrole). All the derivatives were synthesized and tested to determine their photoprotective profile against UV rays, in vitro antioxidant capacity against different radicals (DPPH and FRAP test), antifungal inhibitory activity (dermatophytes and Candida albicans ), antiviral and antiproliferative activity. A Structure-Activity Relationship study indicated compound 10 , bearing a pyrrole heterocycle on the benzimidazole ring, as the best multifunctional derivative of the series and as potential candidate for the development of drugs especially in case of melanoma.

Three series of arylbenzimidazole derivatives 3-40, 45 have been simply synthesized and tested for their antioxidant capacity. The 2-arylbenzimidazoles were tested against various radicals by the DPPH, FRAP and ORAC tests and showed different activity profiles. It has been observed that the number and position of the hydroxy groups on the 2-aryl portion and the presence of a diethylamino group or a 2-styryl group are related to a good antioxidant capacity. Furthermore, benzimidazoles showed satisfactory SPF values ​​in vitro compared to the commercial PBSA filter, proving to have a good photoprotective profile. In particular, 2-arylbenzimidazole-5-sulphonic acids 15 and 38, the 2-styryl-benzimidazole 45 showed broad spectrum solar protection against UVA and UVB rays. The antiproliferative effect of the benzimidazoles was tested on human skin melanoma Colo-38 cells. The styrylbenzimidazole 45 exhibited antiproliferative effect at low micromolar concentration against Colo-38 cells and very low antiproliferative activity on normal HaCat keratinocyte cells., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The incidence of skin cancer is increasing both because of climate change and the increase in pollution than people's incorrect habits of sun exposure. In these regards, sunscreen and photoprotection are essential tools in consenting the benefits induced by safe solar light exposition and skin cancer prevention. In this work, a new class of sunscreen filter was synthesized by chemical combination of a physical filter (ZnO) and Oxisol (dihydroxyphenyl benzimidazole carboxylic acid), an antioxidant molecule with booster effect. In this work, a new class of filters with new properties was achieved by direct functionalization of particles surface. A full characterization of this multifunctional ingredient (ZnO-Ox) was conducted: Compared with the simple mixture, the new filter acts as a multifunctional molecule showing a higher Sun Protection Factor (SPF), a better cytotoxic profile (MTT and NRU assay), and anti-acne activity. A strong reduction of photocatalytic activity of ZnO was observed, also improving the safety profile.

An ever-increasing incidence of skin neoplastic diseases is registered. Therefore, it is important to protect the skin from the UV radiation that reaches the epidermis and dermis but also to block ROS generated by them. Our attention was attracted in developing new compounds provided with both UV filtering and antioxidant capacities. To this end, 2-phenyl-1H-benzimidazole-5-sulfonic acid (PBSA), a known UV filter, was selected as lead compound for its lack of antioxidant activity, high water solubility and good safety profile. PBSA was sequentially modified introducing hydroxyls on the phenyl ring and also substituting the functional group in position 5 of the benzimidazole ring. At the end of the synthetic study, a new, very potent class of antioxidants has been obtained. Surprisingly some of the developed molecules, while devoid of significant UV-filtering activity was endowed with potent UV-filtering booster capability if associated with known commercial UVB and UVA filters.

The synthesis and antiproliferative activity of new benzimidazole derivatives bearing an hydrazone mojety at the 2-position is described. The new N'-(4-arylidene)-1H-benzo[d]imidazole-2-carbohydrazides were evaluated for their cytostatic activity toward the murine leukemia (L1210), human T-cell leukemia (CEM), human cervix carcinoma (HeLa) and human pancreas carcinoma cells (Mia Paca-2). A preliminary structure-activity relationship could be defined. Some of the compounds possess encouraging and consistent antiproliferative activity, having IC50 values in the low micromolar range.

Skin diseases often give multifactorial damages; therefore, the development of multifunctional compounds represents a suitable approach especially against disorders that are induced by oxidative stress. Thus, taking into account the successful results we achieved on benzimidazoles, we have devised a new series of isosteric benzothiazoles and investigated their antioxidant, photoprotective, antifungal and antiproliferative activity. Particular attention has been paid to synergistic antioxidant and photoprotective properties. For compounds 9a and 10a, a multifunctional profile was outlined, supported by an excellent filtering capacity, mainly UVB, which has higher capacities than those of the reference PBSA which is currently in the market as a UV sunscreen filter. The two compounds were also the best in terms of growth inhibition of dermatophytes and Candida albicans, and 10a also showed good antioxidant activity. Furthermore, 9a was also effective on melanoma tumor cells (SK-Mel 5), making these compounds good candidates in the development of new skin protective and preventive agents. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Skin cancer is the most common malignant cancer with an incidence of 1 million cases/year. It is well known that exposure to UV radiation from sunlight leads the most frequent risk factors for several skin disorders including skin cancer. Sunscreen filters represent a valid protection against dangerous effects derived from UV radiation, and they can be divided in organic and inorganic UV filters. Adding, at the product formulation, molecules with booster effect, or also substances that can increase the protecting effectiveness via synergic mechanisms, can further enhance their protection activity. Moreover, this approach leads to develop formulations with high SPF (Sun Protection Factor) with a reduced content of UV filters, this is in line with the recent decisions of yet a few countries (Palau, Thailand, Philippines, and Hawaii) to ban some sunscreen filters to preserve marine environments (i.e., reef). In this work, a new class of sunscreen UV filters has been synthesized, by means the combination of physical filter and Oxisol, an antioxidant molecule with booster effect. In this study, the synthesis of new physical multifunctional ingredients is reported, by means the direct surface functionalization of inorganic filters (in particular TiO2) with Oxisol. In this study, the full characterization of these multifunctional ingredients is also reported, in addition to the cytotoxicity tests, the photocatalytic activity and the rheological properties involved on skin application. [ABSTRACT FROM AUTHOR]