Four Components One-Pot Synthesis of New Thiazoles and Their Biological Screening for Anti-Tuberculosis Activity

Document Type : Research Article


1 Department of Chemistry, Maulana Azad College of Arts, Science and Commerce, Aurangabad-431 003, INDIA

2 Department of Chemistry, Vivekanand ArtsSardar Dalipsingh Commerce and Science College, Aurangabad, Maharashtra 431 001, INDIA


Multi heterocyclic ring system shows a wide spectrum of pharmaceutical and biological activities. Novel series of 2-Benzyloxy-5-(2-{N'-[3-(substituted-phenyl)-1-phenyl-1H-pyrazol-4-ylmethylene]-hydrazino}-thiazol-4-yl)-benzoic acid methyl ester derivatives have been synthesized by one-pot condensation of 2-Benzyloxy-5-(2-bromo-acetyl)-benzoic acid methyl ester, thiosemicarbazide and 3-(substituted-phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde using orthophosphoric acid as a catalyst under mild reaction condition. All the synthesized compounds were screened for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv stains using the Lowenstein-Jensen (L. J.) medium conventional method. Most of these synthesized compounds are found to be active potent against Mycobacterium tuberculosis H37Rv strain. Environmentally benign, multicomponent, rapid, high atom and step economy, facile are the remarkable features
of the present one-pot multicomponent protocol.


Main Subjects

[1] Grobbelaar M., Gail E. L., Samantha L.S., Paul D.V. H., Donald P.R., Warren Robin M., Evolution of Rifampicin Treatment for Tuberculosis , Infection, Genetics and Evolution74: 103937 (2019).
[2] Hassan S.A., Synthesis, Spectroscopic Study and Biological  Activity  of  Some  New  Heterocyclic  Compounds  Derived from  Sulfadiazine, Zanco  Journal  of  Pure  and  Applied Sciences, 31: 92-109.10.21271/ZJPAS.31.6.10 (2019).
[5] Banothu J., Krishnaiah V., Rajitha B., Peter A.C., Sodium Fluoride as an Efficient Catalyst for the Synthesis of 2, 4-Disubstituted-1, 3-Thiazoles and Selenazoles at Ambient TemperatureChinese Chemical Letters 25(1): 172-175 (2014).
[6] Patt W.C., Harriet W. H., Michael D.T., Michael J. R., Tor Jr D.G., Cleo J.C., Annette M.D., Sylvester R.K., Ila S., Structure-Activity Relationships of a Series of 2-Amino-4-Thiazole-Containing Renin InhibitorsJournal of Medicinal Chemistry, 35(14):  2562-2572 (1992).
[7] Kalkhambkar R.G., Kulkarni G.M., Shivkumar H., Nagendra Rao R., Synthesis of Novel Triheterocyclic Thiazoles as Anti-Inflammatory and Analgesic AgentsEuropean Journal of Medicinal Chemistry, 42(10): 1272-1276 (2007).
[8] Jaen Juan C., Wise L.D., Caprathe B.W., Tecle H., Bergmeier S., Humblet C.C., Heffner T.G., Meltzer L.T., Pugsley T.A., 4-(1, 2, 5, 6-Tetrahydro-1-Alkyl-3-Pyridinyl)-2-Thiazolamines: A Novel Class of Compounds with Central Dopamine Agonist Properties, Journal Of Medicinal Chemistry 33(1):  311-317 (1990)
[9] Ergenç N., Çapan G., Günay N.S., Özkirimli S., Güngör M., Özbey S., Kendi E., Synthesis and Hypnotic Activity of New 4‐Thiazolidinone and 2‐Thioxo‐4, 5‐Imidazolidinedione Derivatives,  Archiv der Pharmazie: An International Journal Pharmaceutical and Medicinal Chemistry332(10): 343-347 (1999).
[10] Turan-Zitouni G., Kaplancıklı Z.A., Mehmet T.Y., 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, European Journal of Medicinal Chemistry 40(6): 607-613 (2005).
[11] Sharma R.N., Franklin P. Xavier, Kamala K. Vasu, Subhash C. Chaturvedi, Shyam S. Pancholi. Synthesis of 4-Benzyl-1, 3-Thiazole Derivatives as Potential Anti-Inflammatory Agents: An Analogue-Based Drug Design ApproachJournal of Enzyme Inhibition and Medicinal Chemistry, 24(3): 890-897 (2009).
[12] Bell, Frank W., Amanda S. Cantrell, Marita Hoegberg, S. Richard Jaskunas, Nils Gunnar Johansson, Christopher L. Jordan, Michael D. Kinnick, Peter Lind, and John M. Morin Jr. Phenethylthiazolethiourea (PETT) Compounds,
A New Class of HIV-1 Reverse Transcriptase Inhibitors. 1. Synthesis and Basic Structure-Activity Relationship Studies of PETT Analogs
Journal of Medicinal Chemistry38(25): 4929-4936 (1995).
[13] Karegoudar, Prakash, Mari Sithambaram Karthikeyan, Dasappa Jagadeesh Prasad, Manjathuru Mahalinga, Bantwal Shivarama Holla, and Nalilu Sucheta Kumari. Synthesis of Some Novel 2, 4-Disubstituted Thiazoles as Possible Antimicrobial AgentsEuropean Journal of Medicinal Chemistry43(2): 261-267 (2008).
[14] Hargrave, Karl D., Friedrich K. Hess, and James T. Oliver. N-(4-Substituted-Thiazolyl) Oxamic Acid Derivatives, New Series of Potent, Orally Active Antiallergy AgentsJournal of Medicinal Chemistry, 26(8): 1158-1163 (1983).
[15] Shiradkar, Mahendra, Gorentla Venkata Suresh Kumar, Varaprasad Dasari, Suresh Tatikonda, Kalyan Chakravarthy Akula, and Rachit Shah. Clubbed Triazoles: A Novel Approach to Antitubercular DrugsEuropean journal of medicinal chemistry, 42(6): 807-816 (2007).
[16] Eldred, Colin D., Brian Evans, Sean Hindley, Brian D. Judkins, Henry A. Kelly, John Kitchin, Philip Lumley, Barry Porter, and Barry C. Ross. Orally Active Non-Peptide Fibrinogen Receptor (GpIIb/IIIa) Antagonists: Identification of 4-[4-[4-(Aminoimino Methyl) Phenyl]-1-Piperazinyl]-1-Piperidineacetic Acid as a Long-Acting, Broad-Spectrum Antithrombotic Agent, Journal of Medicinal Chemistry37(23): 3882-3885 (1994).
[17] Amr, Abd El-Galil El-Sayed, Nehad Ahmed Abdel-Latif, Mohamed Mostafa Abdalla. Synthesis of Some New Testosterone Derivatives Fused with Substituted Pyrazoline Ring as Promising 5alpha-Reductase Inhibitors, Acta Pharmaceutica (Zagreb, Croatia), 56(2): 203-218 (2006).
[18] Talley JJ, Donald, Rogier J. Priviledged Synthesis of Pyrazole [1, 3, 4] Thiadiazol-[1, 3, 4] Oxadiazole-2-thione Derivatives, Glob. J. Re.s Anal. 4: 15-6.I. (1995).
[19] Yildirim N., Ozdemir Y., Akcamur M., Dincer O.A., 4-Benzoyl-1, 5-Diphenyl-1H-Pyrazole-3-Carboxylic Acid Methanol Solvate, Hoboken: Wiley; (2005.
[21] Chimichi S., Boccalini M., Hassan M.M.M., Viola G., Dall'Acqua F., Curini M., Synthesis, Structural Determination and Photo-Antiproliferative Activity of New 3-Pyrazolyl Or-Isoxazolyl Substituted 4-Hydroxy-2 (1H)-Quinolinones, Tetrahedron, 62(1): 90-96 (2006).
[22] Radresa O., Paré M., Albert J.S., Multiple Roles of Transient Receptor Potential (TRP) Channels in Inflammatory Conditions and Current Status of Drug Development, Curr. Top. Med. Chem., 13: 367–385 (2013).
[23] Billeter A.T., Hellmann J.L., Bhatnagar A., Polk H.C., Transient Receptor Potential Ion Channels: Powerful Regulators of Cell Function, Ann. Surg., 259: 229–235 (2014).
[24] Tsuchiya H.; Mizogami,M. Comparative Interactions of Anesthetic Alkylphenols with Lipid Membranes, Open J. Anesthesiol., 4: 308–317 (2014).
[25] Bannon A.W., “Current Protocols in Pharmacology”, Wiley: New York, NY, USA, 1–4239 (1998).
[27] Martins M. A.P., Clarissa P. F., Dayse N.M., Lilian B., Pablo M., Solvent-Free Heterocyclic SynthesisChemical Reviews109(9): 4140-4182 (2009).
[28] Mosaddegh E., Hassankhani A., A Rapid, One-Pot, Four-Component Route to 2H-Indazolo [2, 1-b] Phthalazine-TrionesTetrahedron Letters, 52 (4): 488-490 (2011).
[31] Lotfi S., Rahmani T., Hatami M., Pouramiri B., Kermani E.T., Rezvannejad E., Mortazavi M., Hafshejani S.F., Askari N., Pourjamali N., Zahedifar M., Design, Synthesis and Biological Assessment of Acridine Derivatives Containing 1, 3, 4-Thiadiazole Moiety as Novel Selective Acetylcholinesterase Inhibitors, Bioorganic Chemistry, 105: 104457 (2020).
[32] Zahedifar M., Shojaei R., Sheibani H., Convenient Regioselective Reaction in Presence of H3PW12O40: Synthesis and Characterization of Pyrazolo[3,4-B]Quinoline-3,5-Diones, Res. Chem. Intermed., 44: 873–882 (2018).
[33] Azmian Moghadam F., Kefayati H., Evazalipour M.i, Ghasemi S., Design, Synthesis, Biological Evaluation, and Docking Study of Novel 4-Anilinoquinazolines Derivatives as Anticancer Agents, Iranian Journal of Chemistry and Chemical Engineering IJCCE), 41(2): 353-367 (2022).