An Efficient Three Component One-Pot Synthesis of -1,2,3,4-tetrahydro-4-oxo-6- (5-substituted 2-phenyl-1H-indol-3-yl)-2-thioxopyrimidine-5-carbonitrile as Antimicrobial and antitubercular agents

  • Dr. Prabhaker Walmik Sahaydri Science College, Kuvempu University, Shivamogga



Objective: The present study anticipates a novel series of indolyl-pyrimidine derivatives were synthesized by using conventional method. A rapid, improved and eco-friendly synthesis of thiopyrimidines is carried out via one-pot mutlti-component reaction of 5-substituted 2-phenyl-indole-3-carboxaldehydes 1a-c, ethylcyanoacetate 2 and thiourea 3 in the presence of ethanolic K2CO3 under reflux temperature to gave 1,2,3,4-tetrahydro-4-oxo-6-(5-substituted 2-phenyl-1H-indol-3-yl)-2-thioxopyrimidine-5-carbonitriles 4a-c.

Methods: The structures of all these unknown compounds have been confirmed with the help of physical techniques like elemental analysis and melting points. Spectroscopic techniques like IR, 1H & 13C NMR and mass spectral data and these newly synthesized compounds were evaluated for in-vitro antimicrobial and antitubercular activities.

Results: The novel 1,2,3,4-tetrahydro-4-oxo-6-(5-substituted 2-phenyl-1H-indol-3-yl)-2-thioxopyrimidine-5-carbonitriles 4a-c have been synthesized and characterized using spectral and analytical data. Screening studies have demonstrated that the newly synthesized compound 4a exhibited promising antimicrobial and antitubercular properties.

Conclusion: All the newly synthesized compounds were carried out by the broth micro-dilution method (NCCLS. 2002) in a DMF concentration of 500, 250, 125, and 62.5 µg/ml gentamycin and fluconazole are used as reference standards for antibacterial and antifungal activity, respectively. The final results revealed that compound 4a exhibited promising antimicrobial and antitubercular properties when compared to the standard drugs.


Keywords: Keywords: Indole, thioxopyrimidine, antimicrobial, antitubercular activities


1. Ansari KF, Lal C. Synthesis and biological activity of some heterocyclic compounds containing benzimidazole and beta lactam moiety. J Chem Sci 2009; 121:1017-25.
2. Antus S, Gulacsi K, Juhasz L, Kiss L, Kurtan T. Synthesis of naturally occurring o-heterocyclic compounds of biological activity. Pure Appl Chem. 2004; 76:1025-32.
3. Mostafa TB. Synthesis and modification of some heterocyclic compounds with potential biological activity coupled on poly (maleic anhydride–methyl methacrylate). J Am Sci. 2010; 6:512-24.
4. Singh AK, Mishra G, Jyoti K. Review on biological activities of 1,3,4-thiadiazole derivatives. J Appl Pharm Sci. 2011; 1:44-9.
5. Salimon J, Salih N, Hussien H, Yousif E. Synthesis and characterization of new heterocyclic compounds derived from 2-aminopyridine. Eur J Sci Res. 2009; 31:256-64.
6. Xu PF, Zhang ZH, Hui XP, Zhang ZY, Zheng RL. Synthesis of triazoles, oxadiazoles and condensed heterocyclic compounds containing cinchopheny and studies on biological activity of representative compounds. J Chin Chem Soc. 2004; 51:315-9.
7. Bagley MC, Lubinu MC. Microwave-assisted multicomponent reactions for the synthesis of heterocycles. J Heterolic Chem. 2006; 1:31–58.
8. Biswa MS, Ravi Kumar BVV, Jnyanaranjan P, Dinda SC. Ecofriendly and Facile One-Pot Multicomponent Synthesis of Thiopyrimidines under Microwave Irradiation. J Nanoparticles,
9. Misra U, Hitkari A, Saxena AK, Gurtu S, Shanker K. Biologically active indolylmethyl-1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 4H--1,3,4-triazoles and 1,2,4-triazines. Eur J Med Chem. 1996; 31:629-35.
10. Preeti R, Srivastava VK, Ashok KV. Synthesis and anti-inflammatory activity of heterocyclic indole derivatives. Eur J Med Chem. 2004; 39:449-452.
11. El-Gendy Adel A, Abdou Naida A, Sarhan El-Taher Z, El-Banna Hosney AY. Synthesis and biological activity of functionalized indole-2-carboxyates, triazino and pyridazino indoles. Alexandria J Pharm Sci. 1993; 7:99-105
12. Kumar A, Saxena KK, Gurtu S, Sinha JN, Shanker K. Indole alkaloids have been proved to be medicinally important natural durg. Indian Drugs.1986;24: 1-6
13. 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 Letter. 2007; 17(6): 1626–1628.
14. Sureyya O, Dogu N. Synthesis and Biological Evaluation of N- Substituted Indole Esters as Inhibitors of Cyclooxygenase 2 (COX-2). Il Farmaco. 2002; 57(8):677-683.
15. Chen JJ, Wei Y, Williums JD, Drach JC, Townsend LB. Design, synthesis, and antiviral evaluation of some polyhalogenated indole C-nucleosides. Nucleosides, Nucleotides and Nucleic Acids. 2005; 24(10):1417–1437.
16. Baba M. Pauwels R, Herdewijin P, Clerq DE, Desmyter J, Vandeputte M. Both 2',3'-dideoxythymidine and its 2',3'- unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro.Biochem. Biophys. Res. Commun. 1987; 142(1):128-134.
17. Sharma P, Rane N, Gurram VK. Synthesis and QSAR studies of pyrimido[4,5-d] pyrimidine-2,5-dione derivatives as potential antimicrobial agents. Bioorg Med Chem Letters. 2004;14:4185–4190.
18. Ito S, Masuda K, Kusano S. Pyrimidine derivative, process for preparing same and agricultural or horticultural fungicidal composition containing same U.S. Patent 4. 1991; 988: 704.
19. Ram VJ, Haque N, Guru PY. Chemotherapeutic agents XXV: synthesis and leishmanicidal activity of carbazolylpyrimidines, Eur J Med Chem. 1992; 27(8):851–855.
20. Amir M, Javed SA, Kumar H, Pyrimidine as anti-inflammatory agent: a review. Indian J Pharma Sci. 2007; 68:337-441.
21. Vega S, Alonso J, Diaz JA, Junquera F. Synthesis of 3-substituted-4-phenyl-2-thioxo-1,2,3,4,5,6,7,8-octahydrobenzo[4,5]thieno[2,3-d]pyrimidines. J Heterocyl Chem. 1990; 27(2):269–273.
22. El-Kerdawy MM, Yousif Y, El-Emam AA, Moustafa MA, El-Sherbeny MA. Synthesis and antiinflammatory activity of certain thienopyrimidine derivatives. Boll. Chim. Farmaceutico. 1996; 4:301–305.
23. Modica M, Santagati M, Santagati A, Cutuli V, Mangano N, Caruso A. Synthesis of new [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidinone derivatives with antiinflammatory activity. Pharmazie. 2000; 55:500–502.
24. Chambhare RV, Khadse BG, Bobde AS, Bahekar RH. Synthesis and preliminary evaluation of some N-[5-(2-furanyl)-2-methyl-4-oxo-4H-thieno[2,3-d]pyrimidin-3-yl]-carboxamide and 3-substituted-5-(2-furanyl)-2-methyl-3H-thieno[2,3-d]pyrimidin-4-ones as antimicrobial agents. Eur J Med Chem. 2003;38:89–100
25. Santagati NA, Caruso A, Cutuli VM, Caccamo F. Synthsis and phamacological evaluation of thieno[2,3-d]pyrimidin-2,4-dione and 5H-pyrimido[5,4-b]indol-2,4-dione derivatives. IL Farmaco. 1995; 50:689–695.
26. Prabhaker W, Basavaraj SN, Swathi B, Somashekhar G. Design, synthesis of biologically active heterocycles containing indol- thiazolyl- thiazolidinone derivatives. Int J Pharma & Pharmaceutical Sci. 2018; 6:113-117.
27. Prabhaker W, Saundane AR. Synthesis of novel indolyl-thiazolidinone derivatives as antioxidant, antimicrobial and atitubercular agents. . Der Pharm Chem. 2015; 7(6):131-140
28. Prabhaker W, Saundane AR. Synthesis of novel indolyl-azetidinone and thiazolidinone derivatives as a potent antioxidant, antimicrobial and antitubercular agents. Der Pharm Chem. 2014; 6:70-79.
29. Saundane AR, Yarlakatti M, Prabhaker W, Katkar V. Synthesis, antioxidant, antimicrobial, antimycobacterial and cytotoxic activities of azetidinone and thaizolidinone moieties linked to indole nucleus. J Chem Sci. 2012; 124:469-481.
30. Saundane AR, Prabhaker W, Yarlakatti M, Katkar V, Vaijeenath AV. Synthesis and biological activities of some new annulated Pyrazolo pyrano pyrimidines and their derivatives containing indole nucleus. J Het Chem. 2014; 51:303-14.
31. Saundane AR, Prabhaker W, Kirankumar N M, Annapurna H. Synthesis of novel N-(aryl) diazenyl)thiazol-2-amines and bezylidene-thiazolidin-4-ones linked to indole nucleus as antioxidant, antimicrobial, antimycobacterial and Cytotoxic agents. Inter J Pharmacy and Pharmaceutical Sci. (2014); 6(2): 141-147
32. Saundane AR, Prabhaker W. Synthesis, antioxidant, antimicrobial, antimycobacterial and cytotoxic activities of azetidinone and thaizolidinone system linked to indole nucleus. J Chem. 10.1155/2013 /543815
33. Saundane AR, Prabhaker W. Synthesis, Antimicrobial and Antioxidant Activities of Some Indole Analogues containing Naphthyridine and Pyrimidonaphthyridine Systems. J. Chem. 2012; 51B:1593-1606
34. Hiremath SP, Biradar JS, Purohit MG. A new route to indolo [3,2-b] isoquinolines. Indian J Chem. 1982;21B:249-53
35. National Committee for Clinical Laboratory Standards (NCCLS) 940, West Valley Suite 1400, Wayne, Pennsylvania 19087-1898. USA: Performance Standards for Antimicrobial Susceptibility Testing: Twelfth Informational Supplement (ISBN 1-56238-454-6) M100-S12; 2002.
36. Maria CSL, de Souza MVN, Alessandra CP, Marcelle de LF, Raoni SBG, Thais CMN, Monica AP. Evaluation of anti-tubercular activity of nicotinic and isoniazid analogues. ARKIVOK. 2007; 15:181-191
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How to Cite
Dr. Prabhaker Walmik. “An Efficient Three Component One-Pot Synthesis of -1,2,3,4-Tetrahydro-4-Oxo-6- (5-Substituted 2-Phenyl-1H-Indol-3-Yl)-2-Thioxopyrimidine-5-Carbonitrile As Antimicrobial and Antitubercular Agents”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 14, no. 1, Jan. 2021, pp. 94-97,
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