Acyl pyrazole sulfonamides as new antidiabetic agents: synthesis, glucosidase inhibition studies, and molecular docking analysis.

Diabetes mellitus is a multi-systematic chronic metabolic disorder and life-threatening disease resulting from impaired glucose homeostasis. The inhibition of glucosidase, particularly α-glucosidase, could serve as an effective methodology in treating diabetes. Attributed to the catalytic function of glucosidase, the present research focuses on the synthesis of sulfonamide-based acyl pyrazoles (5a-k) followed by their in vitro and in silico screening against α-glucosidase. The envisaged structures of prepared compounds were confirmed through NMR and FTIR spectroscopy and mass spectrometry. All compounds were found to be more potent against α-glucosidase than the standard drug, acarbose (IC50 = 35.1 ± 0.14 µM), with IC50 values ranging from 1.13 to 28.27 µM. However, compound 5a displayed the highest anti-diabetic activity (IC50 = 1.13 ± 0.06 µM). Furthermore, in silico studies revealed the intermolecular interactions of most potent compounds (5a and 5b), with active site residues reflecting the importance of pyrazole and sulfonamide moieties. This interaction pattern clearly manifests various structure-activity relationships, while the docking results correspond to the IC50 values of tested compounds. Hence, recent investigation reveals the medicinal significance of sulfonamide-clubbed pyrazole derivatives as prospective therapeutic candidates for treating type 2 diabetes mellitus (T2DM).

Bioinformatics approach for the construction of multiple epitope vaccine against omicron variant of SARS-CoV-2.

The World Health Organization categorized SARS-CoV-2 as a variant of concern, having numerous mutations in spike protein, which have been found to evade the effect of antibodies stimulated by the COVID-19 vaccine. The susceptibility to omicron variant by immunization-induced antibodies are direly required for risk evaluation. To avoid the risk of arising viral illness, the construction of a specific vaccine that triggers the production of targeted antibodies to combat infection remains highly imperative. The aim of the present study is to develop a particular vaccine exploiting bioinformatics approaches which can target B- and T-cells epitopes. Through this approach, novel epitopes of the S protein-SARS-CoV-2 were predicted for the development of a multiple epitope vaccine. Multiple epitopes were selected on the basis of toxicity, immunogenicity and antigenicity, and vaccine subunit was constructed having potential immunogenic properties. The epitopes were linked with 3 types of linker EAAAK, AAY and GPGPG for vaccine construction. Subsequently, vaccine structure was docked with the receptor and cloned in a pET-28a (+) vector. The constructed vaccine was ligated in pET-28a (+) vector in E. coli using the SnapGene tool for the expression study and a good immune response was observed. Several computational tools were used to predict and analyze the vaccine constructed by using spike protein sequence of omicrons. The current study identified a Multi-Epitope Vaccine (MEV) as a significant vaccine candidate that could potentially help the global world to combat SARS-CoV-2 infections.