Synthesis and in-silico evaluation of some new 2,4-disubstituted thiazole derivatives

Abstract

The synthesis and anti-proliferative activity investigation of methyl 3/4-[[4-(2-substituted thiazol-4-yl)phenyl]amino]-3-oxopropanoate/(4-oxobutanoate) (3a-h) derivatives were aimed in this work. The synthesis of the new compounds were carried out by a simple, multiple-step synthetic procedure. The physicochemical properties of the compounds were determined using SwissADME and QuickProp software systems. Additionally, virtual target and toxicity predictions were carried out for all final compounds. The pharmacokinetics/physicochemical, druglikeness properties and biological target and toxicity predicitions of the compounds were determined to possess satisfying findings. Since the target determination of the compounds according to literature is point out their cytotoxic properties, the DNA gyrase enzyme was chosen as common enzymatic pathway, and evaluated via docking studies. Compound 3b, namely methyl 4-[[4-(2-methylthiazol-4-yl)phenyl]amino]-4-oxobutanoate was detected to possess a potential to inhibit DNA gyrase-ATPase activity.

Keywords

• DNA gyrase inhibition
• druglikeness
• molecular docking
• pharmacokinetic properties
• thiazole

References

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