SYNTHESIS AND EVALUATION OF NEW IMIDAZO[2,1-b]THIAZOLES AS ANTITUBERCULOSIS AGENTS

Abstract

New N’-(arylidene)-2-[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazides (3a-i) were synthesized by reacting 2-[6-(4-bromophenyl)imidazo[2,1-b]thiazol-3-yl]acetohydrazide with different aromatic aldehydes. The structures of the title compounds were established by spectral data (IR, ¹H NMR, ¹³C NMR) and  elemental  analyses.  The   synthesized  compounds  were  evaluated  for  in vitro antimycobacterial activity   against  Mycobacterium tuberculosis  H37Rv  employing  the  BACTEC 460 radiometric system. The   compounds  exhibited  varying  degrees  of   inhibition  in  the  in vitro primary screening  that  was conducted  at  a  concentration  of  6.25 mg/ml.  Among  the  synthesized compounds  [6-(4-bromophenyl) imidazo[2,1-b]thiazol-3-yl]acetic acid  2,4-dinitrobenzylidenehydrazide (3e)  was  found to be the most active compound in vitro with MIC of 6.25 mg/ml.

Keywords

• thiazole,hydrazone,Imidazo,2,1-b

Yeni imidaz o[2,1-b]tiyazol türevlerinin sentezi ve antitüberküler etkilerinin değerlendirilmesi

Abstract

2-[6-(4-Bromofenil)imidazo[2,1-b]tiyazol-3-il]asetohidrazit  ile farklı aromatik aldehitlerin reaksiyonundan yeni N’-  (ariliden)-2-[6-(4-bromofenil)imidazo[2,1-b]tiyazol-3-il]  asetohidrazitler (3a-i) elde edilmiştir. Elde edilen bileşiklerin  yapıları spektral veriler (IR, 1H NMR, 13C NMR) ve elementel  analiz ile saptanmıştır. Sentezlenen bileşiklerin Mycobacterium  tuberculosis H37Rv’ye karşı antimikobakteriyel aktiviteleri  BACTEC 460 radyometrik sistem kullanılarak tayin edilmiştir.  Bileşikler, 6.25 mg/ml konsantrasyonda gerçekleştirilen  in vitro primer tarama testlerinde değişik derecelerde  inhibisyon göstermişlerdir. Sentezlenen bileşikler arasında  [6-(4-bromofenil)imidazo[2,1-b]tiyazol-3-il]asetik asit  2,4-dinitrobenzilidenhidrazit (3e), in vitro 6.25 mg/ml MIC  değeri ile aktivitesi en yüksek bileşik olarak bulunmuştur.  

Keywords

• İmidazo,2,1-b,tiyazol,hidrazon,antimikobakteriyel aktivite

References

1. REFERENCES
2. Tuberculosis; World Health Organization: Geneva, 2014; http://www.who.int/tb/research/en/.
3. Singh MM. XDR-TB-Danger ahead. Indian J Tuberc 2007; 54: 1-2.
4. Remers WA. Antineoplastic Agents. In: Wilson and Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. 10th ed. Delgado JN and Remers WA. eds. Lippincott-Raven: Philadelphia, 1998; p. 391.
5. Andreani A, Granaiola M, Leoni A, Locatelli A, Morigi R, Rambaldi M. Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles. Eur J Med Chem 2001; 36: 743-46.
6. Cesur Z, Güner H, Ötük G. Synthesis and antimycobacterial activity of new imidazo[2,1-b]thiazole derivatives. Eur J Med Chem 1994; 29: 981-83.
7. Park JH, El-Gamal MI, Lee YS, Oh CH. New imidazo[2,1-b]thiazole derivatives: Synthesis, in vitro anticancer evaluation, and in silico studies. Eur J Med Chem 2011; 46: 5769-77.
8. Andreani A, Granaiola M, Guardigli M, Leoni A, Locatelli A, Morigi R, Rambaldi M, Roda A. Synthesis and chemiluminescent high throughput screening for inhibition of acetylcholinesterase activity by imidazo[2,1-b]thiazole derivatives. Eur J Med Chem 2005; 40: 1331-34.

9. Budriesi R, Ioan P, Locatelli A, Cosconati S, Leoni A, Ugenti MP, Andreani A, Di Toro R, Bedini A, Spampinato S, Marinelli L, Novellino E, Chiarini A. Imidazo[2,1-b]thiazole system: A scaffold endowing dihydropyridines with selective cardiodepressant activity. J Med Chem 2008; 51: 1592-1600.
10. Shetty NS, Khazi IAM, Ahn C. Synthesis, anthelmintic and anti-inflammatory activities of some novel imidazothiazole sulfides and sulfones. Bull Korean Chem Soc 2010; 31: 2337-40.
11. Juspin T, Laget M, Terme T, Azas N, Vanelle P. TDAE-assisted synthesis of new imidazo[2,1-b]thiazole derivatives as anti-infectious agents. Eur J Med Chem 2010; 45: 840-45.
12. Wang NY, Xu Y, Zuo WQ, Xiao KJ, Liu L, Zeng XX, You XY, Zhang LD, Gao C, Liu ZH, Ye TH, Xia Y, Xiong Y, Song XJ, Lei Q, Peng CT, Tang H, Yang SY, Wei YQ, Yu LT. Discovery of imidazo[2,1-b]thiazole HCV NS4B inhibitors exhibiting synergistic effect with other direct-acting antiviral agents. J Med Chem 2015; 58; 2764-78.
13. Sah PPT, Peoples SA. Isonicotinyl hydrazones as antitubercular agents and derivatives for identification of aldehydes and ketones. J Am Pharm Ass Sci Ed 1954; 43: 513–24.
14. Isler O, Gutmann H, Straub O, Fust B, Böhni E, Studer A. Chemotherapie der experimentellen Tuberkulose III. Derivate des 2-Methyl-isonicotinsäurehydrazids. Helv Chim Acta 1955; 38: 1046-60.
15. Chakravarty D, Bose A, Bose S. Synthesis and antitubercular activity of isonicotinoyl and cyanoacetyl hydrazones. J Pharm Sci 1964; 53: 1036-39.
16. Thomas KD, Adhikari AV, Telkar S, Chowdhury IH, Mahmood R, Pal NK, Row G, Sumesh E. Design, synthesis and docking studies of new quinoline-3-carbohydrazide derivatives as antitubercular agents. Eur J Med Chem 2011; 46: 5283-92.
17. Küçükgüzel ŞG, Rollas S, Küçükgüzel İ, Kiraz M, Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones. Eur J Med Chem 1999; 34: 1093-1100.
18. Cui Z, Li Y, Ling Y, Huang J, Cui J, Wang R, Yang X. New class of potent antitumor acylhydrazone derivatives containing furan. Eur J Med Chem 2010; 45: 5576-84.
19. Ulusoy N, Çapan G, Ötük G, Kiraz M. Synthesis and antimicrobial activity of new 6-phenylimidazo[2,1-b]thiazole derivatives. Boll Chim Farmac 2000; 139: 167-72.
20. Ulusoy, N. Synthesis and antituberculosis activity of cycloalkylidenehydrazide and 4- aza-1-thiaspiro[4.5]decan-3-one derivatives of imidazo[2,1-b]thiazole. Arzneim- Forsch/Drug Res 2002; 52: 565-71.
21. Ulusoy N, Kiraz M, Küçükbasmacı Ö. New 6-(4-bromophenyl)-imidazo[2,1-b]thiazole derivatives: Synthesis and antimicrobial activity. Monatsh Chem 2002; 133: 1305-15.
22. Ulusoy N, Küçükbasmacı Ö. Synthesis and antimicrobial activity evaluation of new 1,2,4- triazoles and 1,3,4-thiadiazoles bearing imidazo[2,1-b]thiazole moiety. Eur J Med Chem 2010; 45: 63-68.
23. Robert JF, Boukraa S, Panouse JJ, Loppinet V, Chaumont JP. Dérivés de l’imidazo[2,1-b]thiazole X. Propriétés fongistatiques de 2-aminothiazoles et de 6- aryl imidazo[2,1-b]thiazoles substitués respectivement en 4 et en 3 par un reste aryléthyle, aroylméthyle, β-hydroxy β-aryléthyle et et éthoxycarbonylméthyle. Eur J Med Chem 1990; 25: 731-36.
24. Kühmstedt H, Kottke K, Knoke D, Robert JF, Panouse JJ. Synthesis of amides and heterocyclic acylhydrazides with potential immunomodulator properties. Ann Pharm Fr 1983; 40: 425-29.
25. Collins L, Franzblau SG. Microplate alamar blue assay versus BACTEC 460
26. system for high-throughput screening of compounds against Mycobacterium tuberculosis
27. and Mycobacterium avium. Antimicrob Agents Chemother 1997; 41: 1004-9.
28. Inderleid CB.; in: Lorian V. (ed.), Antibiotics in Laboratory Medicine, 3rd ed.,
29. Williams  Wilkins, Baltimore 1991, p. 134.
30. Robert JF., Xicluna A, Panouse JJ. Advances in heterocyclic chemistry. Eur J Med Chem
31. Chim Ther 1975; 10: 59-64.
32. Harraga S, Nicod L, Drouhin JP, Xicluna A, Panouse JJ, Seilles E, Robert JF.
33. Imidazo[2,1-b]thiazole derivatives. XI. Modulation of the CD2-receptor of
34. human T trypsinized lymphocytes by several imidazo[2,1-b]thiazoles. Eur J Med
35. Chem 994; 29: 309-15.
36. Gürsoy E, Ulusoy Güzeldemirci N. Synthesis and primary cytotoxicity evaluation of
37. new imidazo[2,1-b]thiazole derivatives. Eur J Med Chem 2007; 42: 320-26.
38. Çapan G, Ulusoy N, Ergenç N, Kiraz M. New 6-phenylimidazo[2,1-b]thiazole
39. derivatives: Synthesis and antifungal activity. Monatsh Chem 1999; 130: 1399-1407.
40. Gürsoy A, Demirayak Ş, Cesur Z, Reisch J, Ötük G. Synthesis of some
41. hydrazide-hydrazones, thiosemicarbazides, thiadiazoles, triazoles and their derivatives
42. as possible antimicrobiales. Pharmazie 1990; 45: 246-250.