New 4-Thiazolidinones of Nicotinic Acid with 2-Amino-6-methylbenzothiazole and their Biological Activity

The title compounds 6a–j, 2-[(6-methyl-1,3-benzothiazol-2-yl)amino]-N-[2-(substituted phenyl/furan-2-yl)-4-oxo-1,3-thiazolidin-3-yl]nicotinamides, were prepared from 2-chloropyridine-3-carboxylic acid (1) and 2-amino-6-methyl-benzothiazole (2) by known methods. All the compounds have been established by IR, 1H NMR, 13C NMR and elemental analyses. The in vitro antimicrobial screening of the compounds were carried out against two Gram positive (S. aureus, S. pyogenes), two Gram negative (E. coli, P. aeruginosa) bacteria and three fungal species (C. albicans, A. niger, A. clavatus) using the broth microdilution method. Some of the compounds are comparable with standard drugs.


Introduction
A large number of drugs and biologically relevant molecules contain heterocyclic systems.Often the presence of hetero atoms or groupings imparts preferential specificities in their biological responses.The chemistry and biological study of heterocyclic compounds has been interesting field for a long time due to medicinal and agricultural reasons.The number of heterocyclic derivatives containing nitrogen and sulfur atom possess broad Sci Pharm.2010; 78: 753-765.spectrum of biological activities.One of the most important heterocycle in medicinal chemistry is pyridine with wide application including antimicrobial, anti-inflammatory, anti-HIV, antiplasmodial, anti-tubercular, antibacterial and anticonvulsant [1][2][3][4][5][6][7] activities, and has much other important biological significance.The 4-thiazolidinone ring system comprises the broad spectrum for a number of biologically active compounds.In recent years, 4-thiazolidinones are the most extensively investigated class of compounds, which exhibit various biological activities, such as antimicrobial, anti-inflammatory, anti-HIV, anti-toxoplasma gondii and analgesic [8][9][10][11][12].
Looking towards literature, it was thought that incorporation of all these biologically active moieties might be result in better antimicrobial activity and therefore as the part of our continuous research in developing the new heterocycles containing nitrogen and sulfur atom and screening their microbial studies [13][14][15], herewith we have designed 4-thiazolidinones incorporated nicotinic acid with 2-amino-6-methylbenzothiazole and examined their antimicrobial activities.

Investigations, Results and Discussion
The in vitro antibacterial and antifungal activities of the compounds are shown in Table 1.
The MICs (μg/ml) were carried out by broth microdilution method as described by Rattan [17].

Antibacterial Activity
From the screening results (Table 1), it is evident that compound 1 displayed good to moderate activity against all bacteria (150-250 μg/ml).2-Amino-6-methylbenzothiazole (2), compound 3 and hydrazide 4 exhibited moderate to poor activity against all bacteria.

Antifungal Activity
From the results of the antifungal activity (

Conclusion
Most of the compounds are comparable with ampicillin.Compounds bearing -Cl, -NO 2 groups and furan nucleus are more active than the remaining compounds.Compounds 5a, 5d, 5g, 5j, 6b, 6e, 6f and 6j were found to be active against C. albicans but they found poor with other fungal species.

Experimental
All chemicals were of analytical grade and used directly.Melting points of the synthesized compounds were determined by open tube capillary method and were uncorrected.The purity of the compounds was checked by TLC using Merck silica gel 60 F 254 .IR spectra were recorded on a Perkin-Elmer RX 1 FTIR spectrophotometer, using potassium bromide pellets; the frequencies are expressed in cm −1 .The 1 H NMR and 13 C NMR spectra were recorded with a Bruker Avance II 400 NMR spectrometer, using TMS as an internal reference, with DMSO-d 6 as solvent.The chemical shifts are reported in parts per million (δ ppm).Elemental analyses were performed on Carlo Erba 1180 CHN analyzer.All the results of elemental analyses were in an acceptable error range.

Table 1
Results also show that Schiff bases and 4-thiazolidinones possessed good activity against C. albicans while moderate activity against A. niger and A. clavatus.