Synthesis and antimicrobial screening of 5-arylidene-2-imino-4-thiazolidinones

The condensation of 2-aminobenzothiazole-6-carboxylic acid (1) with chloroacetyl chloride in refluxing chloroform in the presence of anhydrous K 2 CO 3 gives 2-(2-chloroacetylamino)benzothiazole-6-carboxylic acid (2) . Compound (2) on treatment with KSCN in refluxing acetone yields 2-(2-imino-4-oxo-thiazolidin-3-yl)benzothiazole-6-carboxylic acid (3) . Compound (3) on condensation with various aromatic aldehydes affords a series of 2-[5-(arylidene)-2-imino-4-oxo-thiazolidin-3-yl]benzothiazole-6-carboxylic acid (4a-h) . The synthesized compounds (4a-h) are screened for their antibacterial as well as antifungal activity. All the tested compounds show slight to moderate activity against the selected microorganisms.


Introduction
Heterocycles bearing nitrogen, sulphur and thiazole moieties constitute the core structure of a number of biologically interesting compounds.The chemistry of thiazolidin-4-one ring systems is of considerable interest as it is a core structure in various synthetic pharmaceuticals displaying a broad spectrum of biological activities. 1 Thiazolidin-4-one derivatives are known to exhibit diverse bioactivities such as antidiarrheal, 2 anticonvulsant, 3 antimicrobial, 4 antidiabetic, 5 antihistaminic, 6 anticancer, 7 antiHIV, 8 Ca 2+ channel blocker, 9 PAF antagonist, 10 cardioprotective, 11 anti-ischemic, 12 cycloxygenase inhibitory, 13 anti-platelet activating factor, 14 non-peptide thrombin receptor antagonist 15 and tumor necrosis factor-α antagonist activities. 168][19] Moreover literature survey reveals that 2-aminobenzothiazoles possess antimicrobial and various other pharmacological activities like diuretic, 20 anticancer, 21 antiulcer, 22 and antihistamine. 23Hence it is thought of interest to accommodate thiazolidin-4-one and 2-amino benzothiazole moieties in single molecular framework and screen them for their antimicrobial activity.

Antibacterial activity
Cup plate method using Hi-Media agar medium is employed to study the antibacterial activity of 4a-h against Staphylococcus aureus, Bacillus subtilis, Psuedomonas aeruginosa and Escherichia coli. 25Preparation of nutrient broth, subculture, base layer medium, agar medium and peptone ARKAT USA, Inc.
water is done as per the standard procedure.Each test compound (50mg) is dissolved in 50 mL of Dimethyl Formamide (1000 µg/mL), which is used as sample solution.Sample size for all the compounds is fixed as 0.1 mL.The cups are made by scooping out agar medium with sterilized cork borer in a petri dish, which is previously inoculated with the microorganisms.The solution of each test compound (0.1 mL) is added in the cups and petri dishes are subsequently incubated at 37 0 for 48 h.Ampicillin and Streptomycin are used as reference drugs and Dimethyl Formamide as a control.Zone of inhibition produced by each compound is measured in mm, as shown in Table 2.
All the newly synthesized compounds show antibacterial activity against S. aureus, B. subtilis, P. aeruginosa and E. coli, the data of which is presented in Table 2.
Thus a series of thiazolidin-4-ones having benzothiazole moiety into one molecular framework have been synthesized which display slight to moderate antibacterial activity.

Antifungal activity
The antifungal activity of compounds 4a-h is tested against four different fungi such as C. albicans, C. pannical, A. niger and R. oryzae by filter paper disc technique 26 .The concentration of test compounds is 1000 µg/mL.After 48 h treatment, zone of inhibition produced by each compound is measured in mm, as shown in Table 3. Griseofulvin is used as the standard antifungal agent and Dimethyl Formamide as a control.All the tested compounds show slight to moderate antifungal activity, the data of which is given in Table 3.

Table 2 .
Antibacterial activity of the compounds 3 and 4a-h
13neral Procedures.Melting points are determined in open capillaries on Thomas Hoover apparatus and are uncorrected.1HNMRand13CNMRspectra are recorded on Bruker AM 400 instrument (at 400 MHz and 300 MHz respectively) using tetramethylsilane (TMS) as an internal standard and DMSO-d 6 as a solvent.Chemical shifts are given in parts per million (ppm).Splitting patterns are designated as follows: s-singlet, d-doublet, t-triplet, q-quartet and mmultiplet.Mass spectra (MS) are recorded on Schimadzu GC-MS.Elemental analysis (C, H, N) is performed on Perkin Elmer 240 analyzer and all compounds are within ±0.4% of theory unless otherwise specified.All products are purified by recrystallisation.The reactions are followed up and the purity of products is carried out on pre-coated TLC plates (Silica gel 60 F 254 , Merck), visualizing the spots in ultraviolet light .Column chromatography is performed on Merck silicagel (60-120 mesh).The antimicrobial screening is carried out at Chemo Test Laboratory.removed in vacuo and the residue is stirred with water (50 mL).The residue is washed with 5% NaHCO 3 and subsequently with water.The crude product is dried and crystallized from methanol to furnish pale yellow solid.Yield (81%); m.p. 160-162 0 C; I.R (KBr, cm -1 ) 3430 ARKAT USA, Inc.(