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Synthesis and Evaluation for Biological Activities of 2-Thio-Acylated Thiazoles Containing Pyrazole Moiety

An approach to the synthesis of novel 2-thio-acylated thiazoles containing pyrazole moiety is described. The pyrazole-thiazolethione derivative as the key building block for bis-heterocycles was formed via a Knoevenagel-type condensation of rhodanine with pyrazol-3-one. Thermal treatment of the pyrazole-thiazolethione derivative with acid anhydride and/or chloride in refluxing toluene caused diacylation reaction to give the corresponding 2-thio-acylated thiazoles containing pyrazole moiety. All the synthesized compounds were characterized by spectroscopic analysis and were tested for their DNA cleavage activity in vitro. Furthermore, they were evaluated for their antifungal activity against Candida albicans and Saccharomyces cerevisiae. Thiazole and related compounds belong to a class of heterocyclic compounds having both a nitrogen and sulfur atom as part of the aromatic five-member ring. Although they have been known from long ago to be biologically active, their varied biological features are still of great scientific interest. Thiazole moiety has been found as an integral part of the structure of therapeutic agents and is widely used like sulfathiazole as antimicrobial agent, ravuconazole as antifungal agent, ritonavir as antiretroviral agent, meloxicam as nonsteroidal anti-inflammatory drug, and antibiotics like penicillin. Moreover, 2-thio-substituted 1,3-thiazoles can be found in a vast number of pharmaceutically active molecules (Figure 1). Hence, their synthesis continues to attract attention and provides an interesting challenge. On the other hand, pyrazole and its derivatives are also an important skeleton found in many synthetic bioactive compounds. Pyrazole derivatives have wide-ranging collection of conventional biological and pharmaceutical activities, such as antitumor, anti-inflammatory, antibacterial, hypoglycemic, and antihypertensive activities. In this context, a large number of general methods for the preparation of pyrazole derivatives have recently been reported. Figure 1. Selected bioactive 2-thio-substituted 1,3-thiazoles In connection with the synthesis of novel thiazoles containing pyrazole moiety, we have reported the novel synthesis of spiro pyrazole derivatives containing cyclobutathiazole moiety starting from pyrazole-thiazolidinone derivative (Scheme 1a). Owing to the importance of thiazoles containing pyrazole moiety, we decided to extend our previous studies to synthesize the pyrazole-thiazole derivatives from pyrazole-thiazolethione derivative as the key substrate, which might have useful biological and therapeutic activities, especially in vitro their DNA cleavage and antifungal activities (Scheme 1b). Scheme 1 cathepsin D inhibitor S N S H N