Synthesis, molecular docking and molecular dynamic simulation studies of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives as antidiabetic agents

Abstract

A series of 2-chloro-5-[(4-chlorophenyl)sulfamoyl]-N-(alkyl/aryl)-4-nitrobenzamide derivatives (5a-5v) has been synthesized and confirmed by physicochemical(R f , melting point) and spectral means (IR, 1 HNMR, 13 CNMR). The results of in vitro antidiabetic study against α-glucosidase indicated that compound 5o bearing 2-CH 3-5-NO 2 substituent on phenyl ring was found to be the most active compound against both enzymes. The electron donating (CH 3) group and electron withdrawing (NO 2) group on a phenyl ring highly favoured the inhibitory activity against these enzymes. The docking simulations study revealed that these synthesized compounds displayed hydrogen bonding, electrostatic and hydrophobic interactions with active site residues. The structure activity relationship studies of these compounds were also corroborated with the help of molecular modeling studies. Molecular dynamic simulations have been done for top most active compound for validating its α-glucosidase and α-amylase inhibitory potential, RMSD analysis of ligand protein complex suggested the stability of top most active compound 5o in binding site of target proteins. In silico ADMET results showed that synthesized compounds were found to have negligible toxicity, good solubility and absorption profile as the synthesized compounds fulfilled Lipinski's rule of 5 and Veber's rule.

Synthesis, in silico studies and biological screening of (E)-2-(3-(substitutedstyryl)-5-(substitutedphenyl)-4,5-dihydropyrazol-1-yl)benzo[d]thiazole derivatives as an anti-oxidant, anti-inflammatory and antimicrobial agents

“…ADMET analysis of synthesized compounds was performed by Molinspiration online tool kit, OSIRIS property explorer and Pre ADMET online server [48][49][50].…”

Investigation of Candidate Genes and Mechanisms Underlying Obesity Associated Type 2 Diabetes Mellitus Using Bioinformatics Analysis and Screening of Small Drug Molecules 

“…Format using open free software from Babel. The co-crystallised protein structures of CEBPD, TP73, ESR2, TAB1 and MAP3K5 of its PDB code 3L4W, 2XWC, 1U3Q, 5NZZ & 2CLQwas extracted from Protein Data Bank 1262 [32][33][34][35][36]. Together with the TRIPOS force eld, GasteigerHuckel (GH) charges were added to all designed derivatives for the structure optimization process.…”

Phytochemical Characterization, Functional Nutrition, and Anti-Diabetic Potentials of Leptadenia hastata (pers) Decne Leaves: In Silico and In Vitro Studies

“…The American Diabetes Association classified diabetes into 2 major categories: Type 1 diabetes (T1D), caused by autoimmune destruction of the β-cell of the pancreas by producing specific antibodies against its cells, 1 and type 2 diabetes (T2D) as a result of a combination of resistance to insulin action and a secretory response by pancreatic β-cells that is inadequate to overcome insulin resistance, leading to relative insulin deficiency. 4 According to WHO data, more than 250 million people are currently living with diabetes, with this figure anticipated to rise to more than 592 million by 2035, 8 with T2D accounting for 80% to 90% of DM. 3 , 4 Astonishingly, a more significant percentage of people with DM are unaware that they have hyperglycemia until it gets to long-term hyperglycemia.…”

“…2 , 10 Management/treatment options for DM range from lifestyle modification, exercise, insulin injection, and use of anti-DM drugs. 5 , 11 The biochemical basis of most anti-DM drugs involves inhibiting the catalytic activities of carbohydrate metabolizing enzymes, such as human pancreatic α-amylase (HPA) and α-glucosidase, which reduces blood sugar levels by suppressing carbohydrate digestion and glucose uptake, 3 , 8 making them the primary targets in controlling blood glucose in DM patients. 12 - 14 Studies have shown that inhibition of HPA is a better suppressor of postprandial hyperglycemia (PPHG) than α-glucosidase because it prevents excessive accumulation of maltose.…”