SYNTHESIS AND BIOLOGICAL ACTIVITIES OF SOME INDOLE ANALOGUES CONTAINING TRIAZOLE-5-THIOL AND THIAZOLOTRIAZOLE SYSTEMS
Keywords:Indole, Triazole-5-thiol, Thiazolotriazole, Antimicrobial, Antioxidant activities
Objective: The present study aims at the synthesis and evaluation of antimicrobial and antioxidant activities of indole analogues incorporated with triazole and thiazolotriazole moieties.
Methods: The newly synthesized compounds were screened for their antimicrobial activity by cup-plate method. Antioxidant activity by three different methods viz.,1,1-diphenyl-2-picryl hydrazil (DPPH) radical scavenging activity (RSA), ferric ion (Fe3+) reducing power (FRAP) and ferrous (Fe2+) ion metal chelating activity were appraised by calorimetric method using UV-Visible spectrophotometer.
Results: The structures of all the newly synthesized compounds have been established on the basis of their IR, 1HNMR, CNMR and mass spectral studies and elemental analysis. Compound 4a showed good radical scavenging activity (RSA), 4b showed good ferric ion (Fe3+) reducing antioxidant power (FRAP) and compounds 3c and 4a exhibited good ferrous ion metal chelating activity. Whereas compound 3b showed good antibacterial activity against P. aeruginosa, 4a against S. aureus and 4c against E. coli. While for the antifungal activity compound 3a was good against A. oryzae, 3c against A. nizer and 4a against A. flavus.
Conclusion: Antimicrobial and antioxidant activity results of the newly synthesized compounds indicate that some of the compounds showed better antimicrobial and antioxidant activities with reference to the standard drugs.
Devasagayam TPA, Tilak JC, Boloor KK, Ketaki S, Saroj SG, Lele RD. Free radicals and antioxidants in human health: current status and future prospects. J Assoc Physicians India 2004;52:785-7.
Athina A, Geronikaki, Antonios M. Antioxidants and inflammatory disease: Synthetic and natural antioxidants with anti-inflammatory ativity. Comb Chem High Throughput Screening 2006;9:425-42.
Deniz S, Hacer B, Ahmet D, Neslihan D, Sengul A. Design and synthesis of new 1,2,4-triazole derivatives containing morpholine moiety as antimicrobial agents. Turkish J Chem 2012;36:411-26.
Gulhan TZ, Zafer AK, Mehmet TY, Pierre C, Demet K. Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives. Eur J Med Chem 2005;40:607-13.
Mali RK, Somani RR, Toraskar MP, Mali KK, Naik PP, Shirodkar PY. Synthesis of some antifungal and antitubercular 1,2,4-triazole analogues. Int J Chem Tech Res 2009;1:168-73.
Krzysztof W, Andrzej G, Jerzy S. Synthesis and antitubercular activity of N-aryl-C-nitroazoles. Eur J Med Chem 2004;39:849-53.
Mari SK. Synthesis, analgesic, anti-inflammatory and antimicrobial studies of 2,4-dichloro-5-fluorophenyl containing thiazolotriazoles. Eur J Med Chem 2009;44:827-33.
Shivarama BH, Narayana KP, Sooryanarayana BR, Shivananda MK. Eur J Med Chem 2002;37:511-7.
Samir B, Wesam K, Ahmed AF. Synthesis and antimicrobial evaluation of some new thiazole, thiazolidinone and thiazoline derivatives starting from 1-chloro-3,4-dihydronaphthalene-2-carboxaldehyde. Eur J Med Chem 2007;42:948-54.
Shivarama BH, Malini KV, Sooryanarayana BR, Sarojini BK, Sucheta NK. Eur J Med Chem 2003;38:313-8.
Paola V, Athina G, Matteo J, Bernadatta B, Graziella P, Carla AC, et al. Synthesis and biological evaluation of benzo[d]isothiazole, benzothiazole and thiazole Schiff bases. Bioorg Med Chem 2003;11:4785-9.
Biao J, Xiao HG. Synthesis and cytotoxicity evaluation of bis(indolyl)thiazole, bis(indolyl)pyrazinone and bis(indolyl)pyrazine: analogues of cytotoxic marine bis(indole) alkaloid. Bioorg Med Chem 2000;8:363-71.
Palmarisa F, Loredana C, Michela P, Riccaro P, Vetrichelvan J, Hiremagalur NJ, et al. Synthesis, conformational analysis and biological activity of new analogues of thiazole-4-carboxamide adenine dinucleotide (TAD) as IMP dehydrogenase inhibitors. Bioorg Med Chem 2005;13:2045-53.
Chang-Ling L, Zheng-ming L, Bin Z. Synthesis and biological activity of novel 2-methyl-4-trifluoromethyl-thiazole-5-carboxamide. J Fluorine Chem 2004;125:1287-90.
Rufine AG, Eric D, Yoan F, Michelle M, Fabrice A, Pascle M. Synthesis and biological activities of aminopyrimidyl-indoles structurally related to meridianins. Bioorg Med Chem 2009;17:4420-4.
James FD, Taro A, Monica E, Bahanu HTD, Joel PB, Peter TM, et al. Synthesis and biological activities of novel aryl indole-2-carboxylic acid analogues as PPAR partial agonists. Bioorg Med Chem 2005;15:5035-8.
Maria KE, Susan L, CarloP, Ulrike B, Antonietta R, Hinnak N, et al. Structural optimization and biological evaluation of 2-substiuted-5-hydroxyindole-3-carboxylates as potent inhibitors of 5-lipoxygenase. J Med Chem 2009;52:3474-83.
Anu A, Kumkum S, Puri SK, Prem MSC. Synthesis of substituted indole derivatives as a new class of antimalarial agents. Bioorg Med Chem Lett 2005;15:3133-6.
Yamamoto Y, Kurazono M. A new class of anti-MRSA and anti-VRE agents: Preparation and antibacterial activities of indole containing compounds. Bioorg Med Chem Lett 2007;17:1626-8.
Mahboobi S, Eichhorn E, Popp A, Sellmer A, Elz S Mollmann U. 3-bromo-4-(1H-3-indolyl)-2,5-dihydro-1H-2,5-pyrrledione derivatives as new lead compounds for antibacterially active substances. Eur J Med Chem 2006;41:176-91.
Ryu CK, Lee JY, Park RE, Ma MY, Nho JH. Synthesis and antifungal activity of 1H-indol-4,7-diones. Bioorg Med Chem Lett 2007;17:127-31.
John DW, John CD, Leroy BT. Synthesis and antiviral activity of some 2-substituted-3-formyl and 3-cyano-5,6-dichloroindole nucleosides. Nucleosides, Nucleotides Nucleic Acids 2005;24:1613-26.
Jiong JC, Yuan W, John DW, John CD, Leroy BT. Design, synthesis and antiviral evaluation of some polyhalogenated indole C-nucleosides. Nucleosides, Nucleotides Nucleic Acids 2005;24:1417-37.
Huifang C, Yanfang Z, Chunshen Z, Ping G. Synthesis and in vitro anti-hepatitis B virus activities of some ethyl-6-bromo-5-hydroxy-1H-indol-3-carboxylates. Bioorg Med Chem 2006;14:911-7.
Renukadevi P, Biradar JS. Synthesis and biological activities of new 3,5-disubstituted-2-(ethyl-5â€™-thioxo-1â€™,3â€™,4â€™-oxadiazol-4â€™-ethylacetate-2â€™-yl)indoles,-2-(5â€™-thioxo-1â€™,3â€™,4â€™-oxadiazol-4â€™-methylcarboxyhydrazide-2â€™-yl)indoles and-2-(5â€™-thioxo-1â€™,3â€™,4â€™-oxadiazol-4â€™-alkyl-2â€™-yl)indoles. Indian J Chem 1999;38B:76-82.
Indian Pharmacopoeia, Government of India, New Delhi. Appendix IV, 3rd edition; 1985.
Hatano T, Kagawa H, Yasuhara T, Okuda T. Two new flavanoids and other constituents in licorice root: their relative astringency and radical scavenging effects. Chem Pharm Bull 1988;36:2090-7.
Oyaizu M. Studies on product of browning reaction prepared from glucose amine. Jpn J Nutr 1986;440:307-16.
Dinis TCP, Maderia VMC, Almeida LM. Action of phenolic derivatives (acetaminophenol, salicylate and 5-amino salicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch Biochem Biophys 1994;315:161-9.