Synthesis and antimicrobial evaluation of novel 2,4-dihydro-3h-pyrazol-3-one hybrids: a new class of antibiotics.

Abstract

The rise in multidrug resistance (MDR) pathogenic microbes has emerged as a critical global health burden. To address this problem, the scientific community and Pharmaceutical industries worldwide are focused in developing newer, safer and cost-effective antimicrobial agents. Design and development of potential antimicrobial agents has been one of the focus areas of the Synthetic and Medicinal Chemistry Research Group (SMCRG), UKZN. In continuation of the ongoing research in SMCRG and the need to discover newer antimicrobials, I envisaged to synthesize novel antimicrobial agents containing 2,4-Dihydro-3H-pyrazol-3-one (pyrazolone) as a core pharmacophoric moiety. Pyrazolones are versatile heterocyclic building blocks and is a core scaffold in several marketed drugs such as for analgesic and antipyretic (phenazone, metamizole, propyphenazon, and remifenazone); neuroprotective agent (edaravon); antispasmodic (dipyron); anti-inflammatory agents (famprofazone, phenylbutazone, and remifenazone) and more recently there have been several reports on the pyrazolone analogs as potential antimicrobial agents. In this research work I have synthesized a series of potential pyrazolone hybrids containing substituted 1,3,4-thiadiazole, thiazolidinone, triazole, oximes, and chalcones as antimicrobial agents (Figure 1). The work in this thesis is divided into 7 chapters: