Synthesis of new pyrazolyl-2, 4-thiazolidinediones as antibacterial and antifungal agents

Abstract

BackgroundThiazolidine-2, 4-diones (TZDs) have become a pharmacologically important class of heterocyclic compounds since their introduction in the form of glitazones into the clinical use for the treatment of type 2 diabetes. TZDs lower the plasma glucose levels by acting as ligands for gamma peroxisome proliferators-activated receptors. In addition, this class of heterocyclic compounds possesses various other biological activities such as antihyperglycemic, antimicrobial, anti-inflammatory, anticonvulsant, insecticidal, etc. TZDs are also known for lowering the blood pressure thereby reducing the chances of heart failure and micro-albuminuria in the patients with type 2 diabetes.ResultsWe have described herein the synthesis of three series of compounds, namely, ethyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (4), methyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (5), and 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetic acids (6). The compounds 4 and 5 were synthesized by Knoevenagel condensation between 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1) and ethyl/methyl 2-(2, 4-dioxothiazolidin-3-yl)acetates (3, 2) in alcohol using piperidine as a catalyst. The resultant compounds 4 and 5 having ester functionality were subjected to acidic hydrolysis to obtain 6. All the new compounds were tested for their in vitro antibacterial and antifungal activity.ConclusionsKnoevenagel condensation approach has offered an easy access to new compounds 4-6. Antimicrobial evaluation of the compounds has shown that some of the compounds are associated with remarkable antifungal activity. In case of antibacterial activity, these were found to be effective against Gram-positive bacteria. However, none of the compounds were found to be effective against Gram-negative bacteria.

Design, synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

“…On the other hand, 3‐benzylthiazolidine‐2,4‐dione ( 7 ) was prepared according to earlier reports. 2,4 Thiazolidinedione was treated with benzyl bromide by using K 2 CO 3 to get the desired product ( 7 ) . Thus, obtained pyrazole‐4‐carbaldehyde ( 4 ) and 3‐benzylthiazolidine‐2,4‐dione ( 7 ) undergo Knoevenagal condensation in toluene using a catalytic amount of piperidine and a few drops of glacial acetic acid refluxing for 8 hours to obtain the intermediate ( 8 ).…”

Design and synthesis of 4′‐((5‐benzylidene‐2,4‐dioxothiazolidin‐3‐yl)methyl)biphenyl‐2‐carbonitrile analogs as bacterial peptide deformylase inhibitors

“…The structure of two biaryl acid compounds 1 (IC 50 = 3.9 μ m ) and 2 (IC 50 = 22.8 μ m ) is presented in Figure . The thiazolidinedione (TZD) scaffold has attracted significant interest of researchers and has become an important class of heterocyclic compounds because of their utility for miscellaneous biological activities including antimicrobial activity . The structure of two antibacterial compounds 3 (MIC range = 6.25–12.5 μ g/mL) and 4 (MIC range = 4.00–128.00 μ g/mL) having TZD scaffold is presented in Figure .…”

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“…That might explain their higher therapeutic potential as opposed to the others in this series. The thiazolidine-dione and its derivatives are popular in anti-diabetic therapeutics 18 , however relatively recent evidences reported its antimicrobial potential, mainly explored against bacteria and fungus 19 .…”