SYNTHESIS, CHARACTERISATION AND ANTI-TUBERCULAR ACTIVITY OF SOME NEW 3,5-DISUBSTITUTED-2,4-THIAZOLIDINEDIONES
As per world health organization by 2020, the number of tuberculosis infected patients will be 25% of the world population. Now, it is challenging and essential target for medicinal chemists in drug search for tuberculosis. Hence the present work includes synthesis of a series of 3,5-disubstituted thiazolidine-2,4-dione derivatives by condensation of thiazolidine-2,4-dione with aromatic aldehydes at 5th position-Knoevenagel reaction followed by condensation of these 5-substituted thiazolidine-2,4-diones by using various aromatic and alkali halides at 3rd position yielding to 3,5-disubstituted thiazolidine-2,4-diones. The synthesized 3,5-disubstituted thiazolidine-2,4-dione compounds were characterized by IR, 1H NMR, Mass spectroscopy and CHNO Elemental analysis. The synthesized compounds were predicted for biological activities by using Prediction of Activity Spectra for Substances computerized program-(Insilico method) based on those results the compounds were screened against Mycobacterium tuberculosis H37RV strain in the Middlebrook 7H9 broth by microplate alamar blue assay using Streptomycin and Pyrazinamide as standard drugs. The results revealed that among those synthesized new 3,5-disubstituted thiazolidinediones 3a, 3b, 3e and 3h were showed good antitubercular activity.
Keywords: Thiazolidine-2,4-dione, knoevenagel reaction, Mycobacterium tuberculosis, antitubercular activity.
Sachin Malik1, Prabhat Kumar Upadhyaya and Sandeep Miglani., Thiazolidinediones: A Plethro of Biological Load. International Journal of Pharm Tech Research 2011; 3(1): 62-75.
Thompson L.A and Ellman J.A., Synthesis and applications of small molecule libraries. Chem. Rev. 1996; 96 (1): 555-600.
Lehmann, J.M., Moore L.B., Smith-Oliver, T.A., Wilkinson, W.O., Willson, T.M and Kliewer, S.A., An antidiabetic thiazolidinedione is a high affinity ligand for Peroxisome Proliferator-activated receptor Î³ (PPARÎ³) J. Bio. Chem. 1995; 270: 12953-56.
Da Ros R, Assaloni R. and Ceriello A., The preventive antioxidant action of thiazolidinediones: a new therapeutic prospect in diabetes and insulin resistance. Diabet. Med. 2004; 21: 1249-52.
Mohammed Iqbal A.K, Ashraf Y. Khan et al., Synthesis, hypoglycemic and hypolipidemic activities of novel thiazolidinedione derivatives containing thiazole/triazole/oxadiazole ring European Journal of Medicinal Chemistry 2012; 53: 308-315.
Bruno G, Costantino C, Maccari R, Monforte F, Ottana R and Vigorita M.G., Synthesis and aldose reductase inhibitory activity of 5-arylidene-2,4-thiazolidinediones. Bioorg. Med. Chem. 2002; 10: 1077-1084.
Suzen S and Buyukbingol E., Recent studies of aldose reductase enzyme inhibition for diabetic complications. Curr Med Chem. 2003; 10(15): 1329-52.
Mulwad V.V, Mir A.A and Parmar H.T., Synthesis and antimicrobial screening of 5-benzylidene-2-imino-3-(2-oxo- 2H-benzopyran-6-yl-)thiazolidine-4-one and its derivatives. Indian J. Chem, 2009; 48B: 137-141.
Kallanagouda R. Alagawadi and Shankar G. Alegaon., Synthesis, characterization and antimicrobial activity evaluation of new 2,4-Thiazolidinediones bearing imidazo[2,1-b][1,3,4]thiadiazole moiety. Arabian Journal of Chemistry. 2011; 4: 465â€“472.
Rekha S, Shantharam U and Vineet chandy., Synthesis and evaluation of novel thiazolidinedione for anti-inflammatory activity., International Research Journal of Pharmacy. 2011; 2(9): 81-84.
F. Herrera, J. C. Mayo, V. MartÃn, R. M. Sainz, I. Antolin and C. Rodriguez., Cytotoxicity and oncostatic activity of the thiazolidinedione derivative CGP52608 on central nervous system cancer cells. Cancer Lett. 2004; 211: 47â€“55.
Naomi Shimazaki, Noriko Togashi et al., Anti-tumour activity of CS-7017, a selective peroxisome proliferator-activated receptor gamma agonist of thiazolidinedione class, in human tumour xenografts and a syngeneic tumour implant model. European Journal of Cancer. 2008, 44, 1734â€“1743.
Ivanna Subtelâ€™na a, Dmytro Atamanyuk et al., Synthesis of 5-arylidene-2-amino-4-azolones and evaluation of their anticancer activity. Bioorganic & Medicinal Chemistry 2010; 18: 5090â€“5102.
Verma A and Saraf SK., 4-thiazolidinone--a biologically active scaffold. Eur J Med Chem. 2008; 43(5): 897â€“905.
Nadia H. Metwally, Nora M. Rateb and Hussein F. Zohdi., A simple and green procedure for the synthesis of 5-arylidene-4-thiazolidinones by grinding. Green Chemistry Letters and Reviews. Sep-2011; 4(3): 225-228.
Magdy Ahmed Ibrahim, Mohamed Abdel-Megid Abdel-Hamed and Naser Mohamed El-Gohary., A new approach for the synthesis of bioactive heteroaryl thiazolidine-2,4-diones, J. Braz. Chem. Soc. 2011; 22(6): 1130-1139.
Maria C. S. Lourenco, Marcus V. N deSouza, Alessandra C Pinheiro, Marcelle de L. Ferreira, Rasnisb B, Goncalves, Thais Cristina M Nogneira and Monica A Peralta, Evaluation of anti-tubercular activity of nicotinic acid isoniazid analogues ARKIVOC. 2007; (xv): 181-191.
How to Cite
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.