Synthesis, molecular docking, toxicity profile and antidiabetic properties of new dipeptide Sulfonamide bearing carboxamides

Sulphonamides are compounds that exhibit a wide range of biological properties and function as therapeutic agents in drug discovery and development. Ten new aryl sulfonamoyl ‘Thr-Gly’ dipeptide carboxamide derivatives were synthesized, characterized and investigated for in vivo antidiabetic properties. The molecular docking study showed some of the synthesized compounds had good binding affinity and established hydrogen bonding interactions in the active site of the protein target. ADMET descriptor was used to calculate and identify toxicity levels of compounds with characteristic pharmacokinetic properties, the result showed they are orally bioavailable and good drug candidates. The physiochemical parameters of the synthesized compounds were in agreement with Lipinski's rule of five. Six compounds displayed antidiabetic potentials, compounds 8c and 8 g had fascinating ability to reduce blood sugar levels significantly higher than the reference drug Glibenclamide. The median lethal dose (LD 50 ) was in the range ≥ 1600 to ≥5000 mg/kg b.w, which showed low toxicity profile. The synthesized compounds exhibited good pharmaceutical potentials and could serve as lead components in developing new anti-diabetic medications. • Diabetes is a major cause of death among the elderly. • Sulfonamides have been reported to possess varying bioactivities. • The new compounds reported herein possessed good antidiabetic activity. • The synthesis of the new molecules are sustainable.