Synthesis and Antimycobacterial Activity of some 2-(4-Aminophenyl)-5-Substitutedamino-1,3,4-thiadiazole Derivatives and Their Coupling Products

Year 2016, Volume: 20 Issue: 2, 199 - 206, 02.02.2016

Sevgi Karakuş , Sevim Rollas

Abstract

In the present study, several 2-(4-aminophenyl)-5-substitutedamino-1,3,4-thiadiazoles (2a-l) and their coupling products, 2,3,4-pentanetrione-3-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]hydrazones (3a-j) were synthesized in good yields and characterized by UV,  IR, ¹H-NMR, mass and elemental analysis. The compounds were evaluated for their in vitro antimycobacterial  activity  against Mycobacterium tuberculosis H37Rv. Antitubercular activity of the synthesized compounds was determined in vitro using the BACTEC 460 Radiometric System against Mycobacterium tuberculosis H37Rv at 6.25 mg/mL. The antimycobacterial data of screened compounds indicated  that 2-(4-aminophenyl)-5-(4-chlorophenyl)amino-1,3,4-thiadiazole demonstra-ted the highest inhibition  (2f ).

 

Keywords

1, 3, 4-thiadiazole, coupling products, antimycobacterial activity

Synthesis and antimycobacterial activity of some 2-(4-aminophenyl)- 5-substituted amino-1,3,4-thiadiazole derivatives and their coupling products

Abstract

References

• 2015 World Health Organization (WHO) Global Tuberculosis Report; http://www.who.int/tb/publications/global_report/gtbr15_main_text.pdf
• Hasan R. Drug resistant tuberculosis: Challenges of urbanization. Int J Mycobacteriol 2014; 3: 79–81.
• Matteelli A, Roggi A, Carvalho AC. Extensively drug-resistant tuberculosis: epidemiology and management. Clin Epidemiol 2014; 6: 111-8.
• Brigden G, Hewison C, Varaine F. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid. Infect Drug Resist 2015; 30(8): 367-78.
• Wong EB, Cohen KA, Bishai WR. Rising to the challenge: new therapies for tuberculosis. Trends Microbiol 2013; 21(9): 493-501.
• Poce G, Cocozza M, Consalvi S, Biava M. SAR analysis of new anti-TB drugs currently in pre-clinical and clinical development. Eur J Med Chem 2014; 86: 335-51.
• Foroumadi A, Soltani F, Moshafi MH, Ashraf-Askari R. Synthesis and in vitro antibacterial activity of some N-(5-aryl-1,3,4-thiadiazole-2-yl)piperazinyl quinolone derivatives. Farmaco 2003; 58: 1023-8.
• Foroumadi A, Kargar Z, Sakhteman A, Sharifzadeh Z, Feyzmohammadi R, Kazemi M, Shafiee A. Synthesis and antimycobacterial activity of some alkyl [5-(nitroaryl)-1,3,4-thiadiazol-2-ylthio]propionates. Bioorg Med Chem 2006; 16: 1164–7.
• Ramprasad J, Nayak N, Dalimba U. Design of new phenothiazine-thiadiazole hybrids via molecular hybridization approach for the development of potent antitubercular agents. Eur J Med Chem 2015; 106: 75-84.
• Rollas S, Karakus, S, Durgun B B, Kiraz M, Erdeniz H. Synthesis and antimicrobial activity of some 1,4-disubstituted thiosemicarbazide and 2,5-disubstituted 1,3,4-thiadiazole derivatives. Farmaco 1996; 51(12): 811-4
• -
• Karakus S, Rollas S. Synthesis and antituberculosis activity of new N-phenyl-N '-[4-(5-alkyl/arylamino-1,3,4-thiadiazole-2-yl)phenyl]thioureas. Farmaco 2002; 57(7): 577-81.
• Rollas S. Reductive cleavage of azo compounds with hydrazine hydrate and some new 1,3,4-thiadiazoles derivatives. J Pharm Univ Mar 1985; 1(1-2): 59-68.
• Inderland CB. in: V. Lorion (Ed.), Antibiotics in Laboratory Medicine, 2nd ed., Williams & Wilkins, Baltimore, 1986, p.181–92.
• Lennette EH, Balows A, Hausler WJ, Shadomy HJ. Manual of Clinical Microbiology, 4th ed., American Society for Microbiology, Washington DC, 1985, p. 59.
• Tatar E, Küçükgüzel ŞG, Karakuş S, Clercq ED, Andrei G, Snoeck R, Pannecouque C, Öktem-Okullu S, Ünübol N, Kocagöz T, Kalaycı S, Şahin F, Küçükgüzel İ. Synthesis and biological evaluation of some new 1,3,4-thiadiazole and 1,2,4-triazole derivatives from L-methionine as antituberculosis and antiviral agents. Marmara Pharm J 2015; 19: 88-102.
• Matysiak J, Opolski A. Synthesis and antiproliferative activity of N-substituted 2-amino-5-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles. Bioorg Med Chem 2006; 14: 4483–9.
• Gülerman NN, Rollas S, Ülgen M, Gorrod JW. Synthesis and evaluation of some substituted 1,3i4-thiadiazole derivatives. Boll Chim Farmaceutica-Anno 1995; 134(8): 461-3.
• Ergenç N, Rollas S, Demir S, Özdemir F. 2-(Acetylacetonylidenehydrazino)-5-chlorobenzophenone and four New Azoles. J Fac Pharm Istanbul 1975; 11: 183-92.
• Küçükgüzel ŞG, Rollas S, Küçükgüzel I, Kiraz M. Synthesis and antimycobacterial activity of some coupling products from 4-aminobenzoic acid hydrazones. Eur J Med Chem 1999; 34: 1093-100.
• Pabuççuoğlu MV, Rollas S. Synthesis and characterization of the coupling products of some diazonium salts with acetylacetone. J Fac Pharm Istanbul 1991; 7(1): 39-49.
• Ergenc N, Rollas S. The Coupling Products of Aliphatic Active C-H Compounds with Diazonium Salts I. J Fac Pharm Istanbul 1975; 11: 8-23.