Experimental and Computational Analysis of Newly Synthesized Benzotriazinone Sulfonamides as Alpha-Glucosidase Inhibitors

Abstract

Diabetes mellitus is a chronic metabolic disorder in which the pancreas secretes insulin but the body cells do not recognize it. As a result, carbohydrate metabolism causes hyperglycemia, which may be fatal for various organs. This disease is increasing day by day and it is prevalent among people of all ages, including young adults and children. Acarbose and miglitol are famous alpha-glucosidase inhibitors but they complicate patients with the problems of flatulence, pain, bloating, diarrhea, and loss of appetite. To overcome these challenges, it is crucial to discover new anti-diabetic drugs with minimal side effects. For this purpose, benzotriazinone sulfonamides were synthesized and their structures were characterized by FT-IR, 1H-NMR and 13C-NMR spectroscopy. In vitro alpha-glucosidase inhibition studies of all synthesized hybrids were conducted using the spectrophotometric method. The synthesized compounds revealed moderate-to-good inhibition activity; in particular, nitro derivatives 12e and 12f were found to be the most effective inhibitors against this enzyme, with IC50 values of 32.37 ± 0.15 µM and 37.75 ± 0.11 µM. In silico studies, including molecular docking as well as DFT analysis, also strengthened the experimental findings. Both leading compounds 12e and 12f showed strong hydrogen bonding interactions within the enzyme cavity. DFT studies also reinforced the strong binding interactions of these derivatives with biological molecules due to their lowest chemical hardness values and lowest orbital energy gap values.

A review on proteolytic fermentation of dietary protein using lactic acid bacteria for the development of novel proteolytically fermented foods

“…Proteolytic bacteria are a type of bacteria that can breakdown proteins into peptides and amino acids, due to their capability to produce protease during fermentation that hydrolyse protein. Proteolytic enzymes are synthesised inside the bacteria cell and are secreted outside the cell into the external environment, or attached to the surface of the cell (Kieliszek et al, 2021). A wide variety of proteolytic microbes such as bacteria, archaea, certain types of algae, and some viruses produce proteases, but most application selects LAB as the candidate.…”

“…Lactobacillus are categorised as nutrient-fastidious bacteria with complex nutritional requirements because they have limited capability to synthesise essential amino acids, nucleotides, and vitamins (Hossain, 2022). Energy for growth is obtained from carbohydrate metabolism, but many cellular constituents including amino acids, sugar, fatty acids, and minerals need to be harvested from the nutrient medium (Kieliszek et al, 2021). Therefore, a nutrient-rich medium is required for their cultivation, where the de Man, Rogosa, and Sharpe (MRS) broth is commonly used as a cultivation medium for laboratory scale.…”

“…Fermented meat products including salami, ham, and sausages, are often consumed in many regions worldwide. During the proteolytic fermentation, sarcoplasmic proteins in meat are hydrolysed to a significant extent, while the myofibrillar and connective tissue proteins are partially hydrolysed (Kieliszek et al, 2021). As a result, the meat turns juicy and tender with higher moisture content and thus improves the digestibility of protein.…”

“…is extensively utilised as a starter culture due to the complex proteolysis system that allows them to breakdown casein into small peptides and free amino acids that contribute to the flavour development and texture improvement in various dairy products. In cheese production, some microbial proteases produced by LAB can replace chymosin, a protease with high specificity for casein, to coagulate milk proteins in the cheese-manufacturing process (Kieliszek et al, 2021). The proteolysis of milk protein enhances the digestibility of products, which is a desirable quality in the infant formula industry.…”

“…The prevalence of hyperglycaemia has dramatically increased during the past two decades and eventually become a major public health concern today. Although synthetic drugs such as metformin, acarbose, quercetin, and resveratrol inhibit α‐amylase and control glucose levels, these synthetic inhibitors could cause undesirable side effects including diarrhoea, flatulence, pain, bloating, and loss of appetite (Khalid et al ., 2022). Many studies have reported the potential of proteolytic fermented food to work as an alternative therapy from a natural source for the management of hyperglycaemia.…”