A new series of twenty-three 1,5-benzodiazepin-2(3H)-ones were synthesized and evaluated in the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), ferric reducing antioxidant power (FRAP), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays as a new chemotype with antioxidant and good drug-like properties. All of the derivatives showed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y and the human hepatoma HepG2 cell lines. Experimental solubility in bio-relevant media showed a good relationship with melting points in this series. Five compounds with the best antioxidant properties showed neuroprotectant activity against H2O2-induced oxidative stress in the SH-SY5Y cell line. From them, derivatives 4-phenyl-1H-1,5-benzodiazepin-2(3H)-one (18) and 4-(3,4,5-trimethoxyphenyl)-1H-1,5-benzodiazepin-2(3H)-one (20) yielded good neuroprotection activity in the same neuronal cell line under 6-OHD and MPP+ insults as in vitro models of mitochondrial dysfunction and oxidative stress in Parkinson’s disease (PD). Both compounds also demonstrated a significant reduction of intracellular Reactive Oxygen Species (ROS) and superoxide levels, in parallel with a good improvement of the Mitochondrial Membrane Potential (ΔΨm). Compared with curcumin, compound 18 better reduced lipid peroxidation levels, malondialdehyde (MDA), in SH-SY5Y cells under oxidative stress pressure and recovered intracellular glutathione synthetase (GSH) levels. Apoptosis and caspase-3 levels of SH-SY5Y under H2O2 pressure were also reduced after treatment with 18. Neuroprotection in neuron-like differentiated SH-SY5Y cells was also achieved with 18. In summary, this family of 1,5-benzodiazepin-2-ones with an interesting antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitutes a new promising chemical class with high potential for the development of new therapeutic agents against PD.

Objective: To assess the in vitro efficacy on antioxidant potential, protection against global oxidative stress, and effect on collagen neosynthesis of minimalist formula (Peptide-C ampoules product) containing 10% natural vitamin C, rice and lupin biopeptides, hyaluronic acid, and Vichy volcanic mineralizing water (active mix). Methods:In-tube quantitative tests ("in-tube screening") assessed global antioxidant properties, anti-lipid peroxidation, anti-protein glycosylation, and metalloproteinase inhibition (anti-collagenase, anti-elastase, and anti-hyaluronidase activity) properties of the formula. Protection against oxidative stress was evaluated on human keratinocyte monolayer cultures, and collagen neosynthesis was quantified on fibroblast monolayer cultures treated with supernatants from product-treated reconstructed human epidermis.Results: Product (5% concentration) showed high antioxidant ability (blocking 99.0% oxidation), protection against oxidative stress damage (51.8% lipid peroxidation and 37.8% protein glycosylation decreases), and inhibition of hyaluronidase (21.9%), elastase (47.1%), and collagenase (61.8%). The protective effect was validated on human keratinocyte monolayer cultures in the presence of active mix (0.025%). Oxidative stress (ROS) was reduced by 99.0%, while global oxidative stress (RMS) induced by pollution, UVA radiation, and a combination of both factors was reduced by 48.94%, 8.7%, and 96.28%, respectively. The product increased collagen neosynthesis (11.21%) by cellular dialogue in fibroblasts incubated with product/mix-treated-RHE supernatants. Conclusion:The combination of ingredients in the product showed high global antioxidant capacity, as well as a protective effect against oxidative stress induced by UVA,This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.