Investigation of the cytotoxicity, genotoxicity and antioxidant prospects of JM-20 on human blood cells: A multi-target compound with potential therapeutic applications.

JM-20 is a 1,5-benzodiazepine compound fused to a dihydropyridine fraction with different pharmacological properties. However, its potential toxic effects on blood cells have not yet been reported. Thus, the present study aimed to investigate, for the first time, the possible cytotoxicity of JM-20 through cell viability, cell cycle, morphology changes, reactive species (RS) to DCFH-DA, and lipid peroxidation in human leukocytes, its hemolytic effect on human erythrocytes, and its potential DNA genotoxicity using plasmid DNA in vitro. Furthermore, the compound's ability to reduce the DPPH radical was also measured. Human blood was obtained from healthy volunteers (30 ± 10 years old), and the leukocytes or erythrocytes were immediately isolated and treated with different concentrations of JM-20. A cytoprotective effect was exhibited by 10 µM JM-20 against 1 mM tert-butyl hydroperoxide (t-but-OOH) in the leukocytes. However, the highest tested concentrations of the compound (20 and 50 µM) changed the morphology and caused a significant decrease in the cell viability of leukocytes (p < 0.05, in comparison with Control). All tested concentrations of JM-20 also resulted in a significant increase in intracellular RS as measured by DCFH-DA in these cells (p < 0.05, in comparison with Control). On the other hand, the results point out a potent antioxidant effect of JM-20, which was similar to the classical antioxidant α-tocopherol. The IC50 value of JM-20 against the lipid peroxidation induced by (FeII) was 1.051 µM ± 0.21, while the IC50 value of α-tocopherol in this parameter was 1.065 µM ± 0.34. Additionally, 50 and 100 µM JM-20 reduced the DPPH radical in a statistically similar way to the 100 µM α-tocopherol (p < 0.05, in comparison with the control). No significant hemolysis in erythrocytes, no cell cycle changes in leukocytes, and no genotoxic effects in plasmid DNA were induced by JM-20 at any tested concentration. The in silico pharmacokinetic and toxicological properties of JM-20, derivatives, and nifedipine were also studied. Here, our findings demonstrate that JM-20 and its putative metabolites exhibit similar characteristics to nifedipine, and the in vitro and in silico data support the low toxicity of JM-20 to mammals.

Development of a nanotechnological-based hydrogel containing a novel benzofuroazepine compound in association with vitamin E: An in vitro biological safety and photoprotective hydrogel.

This study aimed to evaluate the potential DNA photoprotection of nano-based hydrogels containing a novel benzofuroazepine molecule. Photoprotective property of three benzofuroazepine derivative compounds was assessed by determining a UV light absorptive profile. Nanocapsule suspensions (Eudragit® RS 100 as polymeric wall and medium-chain triglyceride or vitamin E as oil core) containing the benzofuroazepine compound that had the best UV spectral absorption were developed and physicochemically characterized. Photostability assay, bioadhesive property as well as preliminary toxicity parameters (HET-CAM and Artemia salina lethality assays) for free or nanoencapsulated forms were assessed. Among the molecules, the UV absorbance spectrum of free MBBA showed a broad and high intensity absorbance at UVB and UVA ranges. MBBA-nanocapsule suspensions had nanometric and homogeneous size distribution, bioadhesiveness property, and increased the UV light scattering in comparison to the free compound. Besides, all formulations triggered no irritative responses and the nanoencapsulation mitigated the toxic effect to Artemia salina observed to free MBBA. Following, hydrogels were prepared by thickening nanocapsule suspensions with gellan gum and their DNA photoprotection properties were determined by the exposure of DNA samples to the UVB and UVA radiation. Hydrogels showed acid pH values, compound content close to the theoretical value (3 mg/g), particle size in nanometric range, and spreadability profile suitable for cutaneous application. All MBBA hydrogels were effective against photoproducts formation induced by UVB and UVA radiation. In conclusion, these data show the identification of a compound with promising UV absorptive potential and the preparation of a final nano-based hydrogel for cutaneous application.