Synthesis and biological activity of some new 4-thiazolidinone derivatives

•t 4-Thiazolidinone is a medicinally important moiety. We have used thiourea with other potential moiety 4-quinazolinone to enhance medicinal value of the 4-thiazolidinones moiety. 15 new compounds are reported along with their spectral data, antibacterial and antitubercular activities.

4-Thiazolidinones have been found to be endowed with a variety of biological activities l-S. Keeping in view the medicinal importance and utility of thiazolidine moiety, it was worth attempting to synthesize some new potential 4oxothiazolidines in which the side chain of actithiazic acid in position-2 is shifted to position-S in 4-thiazolidinone with substituting other groups in the ring. In the present paper, we have incorporated well-known organic synthon thiourea with another potential moiety 4-quinazolinone to augment medicinal value of the compounds. All the new compounds were screened for their antibacterial and antitubercular activities.

Results and discussion
Biological activity : The compounds· were screened for antibacterial activity using cup-plate method 6 . The testing was carried out in DMF solution at a concentration of 50 )..lg mt-1 using gram positive bacteria like Staphylococcus aureus and gram negative bacteria like Escherichia coli and Salmonella typhosa. Chloramphenicol was used as a standard drug.

Antitubercular activity of the synthesized compounds :
This activity was carried out at TAACF (Tuberculosis Antimicrobial Acquisition and Coordinating Facility), Southern Research Institute, Birmingham, Alabama. The following procedure was used. The TAACF integrates the various components of the drug discovery and development process into a unified program that facilitates the search for antimycobacterial drugs. This program consists of four closely interwoven components; a compound acquisition, repository, and data analysis service operated where, Ar =different aryl groups cited in Table I.
Under the direction of the U.S. National Institute of Allergy and Infectious Diseases (NIAID), Southern Research Institute coordinates the overall program. All services are provided confidentially and at no cost to the supplier.
In vitro evaluation of antimycobacterial activity : Primary screening conducted at 12.50 )..lg mt-1 (or molar equivalent of highest molecular weight compound in a series of congeners) against Mycobacterium tuberculosis H 37 Rv (ATCC 27294) in BACTEC 128 medium using a broth microdilution assay, the Microplate Alarnar Blue Assay (MABA) 7 . Compounds exhibiting fluorescence are tested in the BACTEC 460 radiometric system. Compounds effecting <90% inhibition in the primary screen (i.e., MIC > 12.50 )-l.g ml-1 ) arc not generally evaluated further.

Experimental
All melting points were taken in open capillaries and are uncorrected. The structures of the new products were confirmed by the elemental and spectral analysis. IR spectra (KBr) were recorded on a Shimadzu FTIR spectrophotometer, 1 H NMR spectra (CDC1 3 + TFA) on Bruker (200 MHz) and Hitachi 1200 (60 MHz) spectrometers using TMS as internal reference and mass spectra on a Jeol JMSD-300 spectrometer.