Synthesis, α-Glucosidase inhibitory activity and docking studies of Novel Ethyl 1,2,3-triazol-4-ylmethylthio-5,6-diphenylpyridazine-4-carboxylate derivatives.

In this work, a novel series of pyridazine-triazole hybrid molecules were prepared and evaluated as inhibitors of rat intestinal α-glucosidase enzyme. Amongst all newly synthesized compounds, 10k showed good inhibition in the series with IC50 value of 1.7 µM which is 100 folds stronger than positive control, acarbose. The cytotoxicity revealed that this compound is not toxic against normal cell line, HDF. The docking studies showed that triazole ring plays an important role in the binding interactions with the active site. The insertion of compound 10k into the active pocket of α-glucosidase and formation of hydrogen bonds with Leu677 was observed from docking studies. The kinetic studies revealed that this compound has uncompetitive mode of inhibition against α-glucosidase enzyme.

The expression of ACAT1 in oral squamous cell carcinoma and the adjacent pre-tumour tissue.

Background: Altered acetyl CoA acetyltransferase 1 (ACAT1) expression has been reported in diverse cancers. However, the expression of ACAT1 and its prognostic value in oral squamous cell carcinoma (OSCC) has remained unexplored. Materials and methods: In this study, the expression of ACAT1 was analysed by immunohistochemistry (IHC) in 61 OSCC patients and compared between OSCC and adjacent pre-tumour tissue of 21 patients. Results: The expression of ACAT1 in OSCC tumours is heterogeneous between patients. More specifically, 52.38% of the patients show low expression of ACAT1 in both tumour and adjacent pre-tumour tissues, 9.52% of the patients show high expression of ACAT1 in both tumour and adjacent pre-tumour, 19.05% of the patients have high expression of ACAT1 in tumour tissue and low expression of ACAT1 in adjacent pre-tumour tissue and another 19.05% of the patients have low expression of ACAT1 in tumour tissue and high expression of ACAT1 in adjacent pre-tumour tissue. Conclusion: Comparison of ACAT1 expression, one of the key enzymes in the ketone body metabolic pathway, divided OSCC patients into two groups: 1) similar expression and 2) different expression of ACAT1 in tumour and adjacent pre-tumour tissue. No significant association between ACAT1 levels and overall survival was observed.