Synthesis, molecular docking studies, and absorption, distribution, metabolism, and excretion prediction of novel sulfonamide derivatives as antibacterial agents

Abstract

A series of novel sulfonamide-amide derivatives were synthesized from 3-(2,4 dichlorophenylamino)-3-oxopropane-1-sulfonylchloride and a variety of amines under solvent-free conditions at room temperature. 3-(2,4-dichlorophenylamino)-3-oxopropane-1 sulfonylchloride was synthesized in four steps starting from 2,4-dichloroaniline and chloropropanoic acid in good yield and purity. The synthesized compounds were screened for their in vitro antibacterial activity against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213). Molecular docking of sulfonamide derivatives into S. aureus tyrosyl-tRNA synthetase (TyrRS)-active site was also performed and among these, 5m and 5g tightly fit the active sites that might be inhibitors of TyrRS for further investigations. Also in the silico metabolism profile, drug-like properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) of the title compounds were calculated by the preADMET server. K E Y W O R D S

Synthesis of some novel coumarin isoxazol sulfonamide hybrid compounds, 3D-QSAR studies, and antibacterial evaluation

“…A mixture of SOCl 2 (4.8 mmol) and 2-oxo-2H-chromene-3-carboxylic acid (4 mmol) was stirred for 12 h at 75 ºC. After extra SOCl 2 distillation , high purity light yellow solid product was obtained; M.p = 158–160 °C (M.p Lit = 158–161 °C) 45 .…”

“…In continuance of our works on the synthesis and computational studies of small biologically active compounds 40 – 45 , 3D-QSAR models were performed to predict novel coumarin Isoxazol sulfonamide hybrids possible MIC on the bacteria. Also, the antibacterial activity of the designed and synthesized sulfonamides hybrids was assessed.…”