Design, Synthesis, Docking and Computational Pharmacokinetic Profiling of New Pyrazolinyl Thiazolinone Biheterocycles as Potent Antimicrobial Agents

Abstract

Background: Development of potential antimicrobial agents is the main aim in the drug discovery process to overcome the problem of drug resistance. Pyrazolines and thiazolinones are extensively used as building blocks for the synthesis of diverse and medicinally important compounds. Methods: In this present work, a new series of functionalized pyrazolinyl-thiazolinone biheterocycles is designed and synthesized from N-pyrazolinecarbothioamide. Antimicrobial screening is carried out in order to discover their potential towards six bacterial and four fungal strains. The zone of inhibition (ZI in mm) was determined by the disc diffusion method and minimum inhibitory concentration (MIC in μg/mL) by macro dilution method. The druggability of these new entities is done through in silico pharmacokinetic profiling using Maestro 2017-1 interface of Schrӧdinger software. Results and Disscusion: Compounds 4c and 4e with chloro and iodo substituents on Nphenylacetamide ring displayed good inhibitory antibacterial activity against the tested bacterial strains with minimum MIC values when compared to the reference drug tetracycline. Compound 3 with an acetic acid derivative showed high antifungal activity among all the tested derivatives. Compound 3 not only showed antifungal activity but also qualified druggability test with no violation of Lipinski rule of five. Conclusion: The capability of the synthesized pyrazolinyl-thiazolinone derivatives was performed to efficiently inhibit the growth of microorganisms against selected bacterial and fungal strains. Further, these compounds are found to be effectively bound to the active sites of attractive target Escherichia coli FabH.