In vitro, in silico and Pharmaco-toxicological Efficiencies of some Triazole Derivatives on Inhibition of Digestive Enzyme Alpha-amylase

Obesity is one of the main health problems associated with a range of diseases. Genetic disposition is related to the risk for obesity but external conditions such lifestyle also increase the incidence. Current COVID-19 pandemic conditions around the globe have been reported to increase the cases of Type-2 diabetes mellitus (T2DM) due to prolonged sedentary life. Among the various treatment modalities, applications of alpha-amylase inhibitors are commonly used worldwide. Commercially available anti-diabetic drugs are potent inhibitors of alpha-amylase that reduce postprandial hyperglycemia. In this study, alpha-amylase inhibition efficiencies of some 1,2,4-triazole derivatives were evaluated. Furthermore, it has been attempted to determine the possible inhibition mechanism of the strongest inhibitor compound among the 8 candidate molecules for alpha-amylase. Compound VII showed the strongest inhibition on alpha-amylase activity with low IC50 value (150 mu M). An inhibitory kinetic analysis on alpha-amylase activity by Compound VII was found to be reversible and uncompetitive. Furthermore, molecular docking studies with this molecule showed that it could bind to the catalytic site of the enzyme by performing weak interactions with Ser56, Tyr59, Tyr62, Asp176, Asp274 and Leu142 residues. Cytotoxic potential of Compound VII on amylase overexpressing AR42J pancreatic cancer cells was also performed using trypan blue staining and the compound at the highest dose 10 mu M was found to be cytotoxic, but effective for alpha amylase inhibition at non-cytotoxic doses. The results showed in vitro effect of Compound VII on alpha-amylase inhibition in cells. Here, we suggest an alternative and non-cytotoxic alpha-amylase inhibitor for T2DM.

Cytotoxic effect of a 3-(4-chlorophenyl)-5-(4-methoxybenzyl)-4H-1,2,4-triazole derivative compound in human melanoma cells

Melanoma represents the most forceful derm cancer with a high rate of mortality. Although chemotherapy has been commonly used in the treatment of melanoma, drug resistance and side effects of conventional chemotheurapeutics negatively affect the continuity and success the treatment. 1,2.4 triazole derivatives are popular compounds of recent years with anti-microbial, anti-inflammatory, analgesic, antiviral, anti-proliferative and COVID-19 associated anti-fungal activities. However, studies that revealed the effects of 1,2.4 triazole compounds on melanoma cells are limited. The aim of this study was to investigate the effects of a 3-(4-chloropheny1)-5-(4-methoxybenzy1)-4H-1,2.4-triazole derivative (B9) compound on cytotoxicity and cell cycle using MTT and flow cytometrv, respectively and the inhibitory' effect on tyrosinase in human melanoma (VMM917) cells using colorimetric assay for melanin content. The compound B9 exhibited a selective cytotoxic effect (4.9-fold) on VMM917 cells compared to normal cells. B9 induced cell cycle arrest at the S phase and also decreased the amount of melanin in the cells. The results suggest a novel candidate drug in melanoma therapy. The detailed investigation of the molecular mechanism of this selective cytotoxic effect will provide understanding on the usability of B9 as an alternative chemotherapeutic agent in melanoma.