Triazole: A Promising Antitubercular Agent

Tuberculosis is a contagious disease with comparatively high mortality worldwide. The statistics shows that around three million people throughout the world die annually from tuberculosis and there are around eight million new cases each year, of which developing countries showed major share. Therefore, the discovery and development of effective antituberculosis drugs with novel mechanism of action have become an insistent task for infectious diseases research programs. The literature reveals that, heterocyclic moieties have drawn attention of the chemists, pharmacologists, microbiologists, and other researchers owing to its indomitable biological potential as anti‐infective agents. Among heterocyclic compounds, triazole (1,2,3‐triazole/1,2,4‐triazole) nucleus is one of the most important and well‐known heterocycles, which is a common and integral feature of a variety of natural products and medicinal agents. Triazole core is considered as a privileged structure in medicinal chemistry and is widely used as ‘parental’ compounds to synthesize molecules with medical benefits, especially with infection‐related activities. In the present review, we have collated published reports on this versatile core to provide an insight so that its complete therapeutic potential can be utilized for the treatment of tuberculosis. This review also explores triazole as a potential targeted core moiety against tuberculosis and various research ongoing worldwide. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic triazole‐based antituberculosis drugs.

[1]  A. Ullrich,et al.  Interplay between mycobacteria and host signalling pathways , 2004, Nature Reviews Microbiology.

[2]  L. Schlesinger Macrophage phagocytosis of virulent but not attenuated strains of Mycobacterium tuberculosis is mediated by mannose receptors in addition to complement receptors. , 1993, Journal of immunology.

[3]  H. K. Reitze,et al.  Environmental actions of agrochemicals 1. Side-effects of the herbicide 3-amino-1,2,4-triazole on a laboratory acarine/host-plant interaction (Tetranychus urticae/Phaseolus vulgaris) as revealed by electron microscopy , 2005, Experimental & Applied Acarology.

[4]  S. Larson,et al.  Growth inhibition and induction of cellular differentiation of human myeloid leukemia cells in culture by carbamoyl congeners of ribavirin. , 1990, Journal of medicinal chemistry.

[5]  P. Yogeeswari,et al.  Efficient synthesis and in vitro antitubercular activity of 1,2,3-triazoles as inhibitors of Mycobacterium tuberculosis. , 2011, Bioorganic & medicinal chemistry letters.

[6]  G. Szilágyi,et al.  1,2,4-triazole derivatives , 1985 .

[7]  W. Burman Rip Van Winkle wakes up: development of tuberculosis treatment in the 21st century. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  N. Jagadeesh Babu,et al.  Anti-tubercular agents. Part 8: synthesis, antibacterial and antitubercular activity of 5-nitrofuran based 1,2,3-triazoles. , 2013, Bioorganic & medicinal chemistry letters.

[9]  G. Besra,et al.  Identification of arylamine N-acetyltransferase inhibitors as an approach towards novel anti-tuberculars , 2010, Protein & Cell.

[10]  R. Kharb,et al.  Pharmacological significance of triazole scaffold , 2011, Journal of enzyme inhibition and medicinal chemistry.

[11]  A. Lourenço,et al.  Synthesis, antitubercular activity, and SAR study of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides. , 2011, Bioorganic & medicinal chemistry.

[12]  David M. Shackleford,et al.  Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. , 2009, Journal of medicinal chemistry.

[13]  G. Shenoy,et al.  Synthesis and in‐vitro antimicrobial activity of new 1,2,4‐triazoles , 2001, The Journal of pharmacy and pharmacology.

[14]  D. Russell Mycobacterium tuberculosis and the intimate discourse of a chronic infection , 2011, Immunological reviews.

[15]  Shamim Ahmad,et al.  Bioactive Triazoles : A potential review , 2013 .

[16]  M. Pasca,et al.  Chemical synthesis and biological evaluation of triazole derivatives as inhibitors of InhA and antituberculosis agents. , 2012, European journal of medicinal chemistry.

[17]  Ş. Küçükgüzel,et al.  Some 3-thioxo/alkylthio-1,2,4-triazoles with a substituted thiourea moiety as possible antimycobacterials. , 2001, Bioorganic & medicinal chemistry letters.

[18]  C. Dye,et al.  The Population Dynamics and Control of Tuberculosis , 2010, Science.

[19]  K. Chai,et al.  Synthesis of some quinoline-2(1H)-one and 1, 2, 4 - triazolo [ 4 , 3 -a ] quinoline derivatives as potent anticonvulsants. , 2007, Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques.

[20]  J. Ernst,et al.  Tuberculosis pathogenesis and immunity. , 2012, Annual review of pathology.

[21]  M. Radi,et al.  Synthesis and biological evaluation of new enantiomerically pure azole derivatives as inhibitors of Mycobacterium tuberculosis. , 2009, Bioorganic & medicinal chemistry letters.

[22]  V. Mokale,et al.  Synthesis of new S-derivatives of clubbed triazolyl thiazole as anti-Mycobacterium tuberculosis agents. , 2007, Bioorganic & medicinal chemistry.

[23]  Supriya Gupta,et al.  Synthesis and in vitro study of some fused 1,2,4-triazole derivatives as antimycobacterial agents , 2016 .

[24]  E. AUGUSTYNOWICZ-KOPEĆ,et al.  Synthesis and Tuberculostatic Activity of Some 2-Piperazinmethylene Derivatives 1,2,4-Triazole-3-Thiones , 2005 .

[25]  S. Lawn,et al.  Extensively drug resistant tuberculosis , 2006, BMJ : British Medical Journal.

[26]  P. G. Nayak,et al.  Click Chemistry Approach for Bis‐Chromenyl Triazole Hybrids and Their Antitubercular Activity , 2012, Chemical biology & drug design.

[27]  V. Berestovitskaya,et al.  Synthesis of 4-Aryl-5-nitro-1,2,3-triazoles , 2004 .

[28]  Z. Kaplancıklı,et al.  Synthesis and antituberculosis activity of new 3-alkylsulfanyl-1,2,4-triazole derivatives , 2005, Journal of enzyme inhibition and medicinal chemistry.

[29]  P. Yogeeswari,et al.  Syntheses and biological evaluation of new triazole-spirochromone conjugates as inhibitors of Mycobacterium tuberculosis , 2011 .

[30]  I. Smith,et al.  Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence , 2003, Clinical Microbiology Reviews.

[31]  K. Banu,et al.  Synthesis, Characterization, Antimicrobial Studies And Pharmacological Screening Of Some Substituted 1,2,3-Triazoles , 1999 .

[32]  J. Montana,et al.  Synthesis and evaluation of a novel series of phosphodiesterase IV inhibitors. A potential treatment for asthma. , 1998, Bioorganic & medicinal chemistry letters.

[33]  P. Yogeeswari,et al.  Design, synthesis, and structure-activity correlations of novel dibenzo[b,d]furan, dibenzo[b,d]thiophene, and N-methylcarbazole clubbed 1,2,3-triazoles as potent inhibitors of Mycobacterium tuberculosis. , 2012, Journal of medicinal chemistry.

[34]  G. V. Suresh Kumar,et al.  Clubbed triazoles: a novel approach to antitubercular drugs. , 2007, European journal of medicinal chemistry.

[35]  Ming-Der Chen,et al.  Synthesis and Antibacterial Activity of some Heterocyclic β-Enamino Ester Derivatives with 1,2,3-triazole , 2000 .

[36]  M. Alam,et al.  Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents. , 2014, European journal of medicinal chemistry.

[37]  P. Chevallet,et al.  Synthesis of some 4-arylidenamino-4H-1,2,4-triazole-3-thiols and their antituberculosis activity , 2007, Journal of enzyme inhibition and medicinal chemistry.

[38]  Â. Pinto,et al.  Novel 1,2,3-triazole derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) strain. , 2011, Journal of medicinal chemistry.

[39]  Kazuo Kobayashi,et al.  [Recent progress in mycobacteriology]. , 2007, Kekkaku : [Tuberculosis].

[40]  S. Cao,et al.  Synthesis and insecticidal activity of 1,2,4-triazole derivatives , 2003 .

[41]  P. Yogeeswari,et al.  Design, synthesis and evaluation of 1,2,3-triazole-adamantylacetamide hybrids as potent inhibitors of Mycobacterium tuberculosis. , 2014, Bioorganic & medicinal chemistry letters.

[42]  N. Patel,et al.  Pharmacological Evaluation and Characterizations of Newly Synthesized 1,2,4‐Triazoles. , 2011 .

[43]  Abdel-Rhman B. A. El-Gazzar,et al.  Synthesis and evaluation of analgesic, anti-inflammatory and ulcerogenic activities of some triazolo- and 2-pyrazolyl-pyrido[2,3-d]-pyrimidines , 2008, Acta pharmaceutica.

[44]  Ying Zhang,et al.  New drug candidates and therapeutic targets for tuberculosis therapy. , 2006, Drug discovery today.

[45]  N. Tawari,et al.  Novel 4H-1,2,4-triazol-3-yl cycloalkanols as potent antitubercular agents , 2012, Medicinal Chemistry Research.

[46]  E. Garvey,et al.  The use of oxadiazole and triazole substituted naphthyridines as HIV-1 integrase inhibitors. Part 1: Establishing the pharmacophore. , 2009, Bioorganic & medicinal chemistry letters.

[47]  Bharathkumar Inturi,et al.  Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4-triazoles as potential antitubercular agents. , 2014, European journal of medicinal chemistry.

[48]  E. De Clercq,et al.  In search of a selective antiviral chemotherapy , 1997, Clinical microbiology reviews.

[49]  K. T. Potts,et al.  The Chemistry of 1,2,4-Triazoles. , 1961 .

[50]  R. Gambari,et al.  Pyrazolo-triazoles as light activable DNA cleaving agents. , 2000, Bioorganic & medicinal chemistry.

[51]  J. Frère,et al.  NH-1,2,3-Triazole-based Inhibitors of the VIM-2 Metallo-β-Lactamase: Synthesis and Structure-Activity Studies. , 2010, ACS medicinal chemistry letters.

[52]  N. Patel,et al.  Antimycobacterial and antimicrobial study of new 1,2,4‐triazoles with benzothiazoles , 2010, Archiv der Pharmazie.

[53]  C. Gill,et al.  SAR study of clubbed [1,2,4]-triazolyl with fluorobenzimidazoles as antimicrobial and antituberculosis agents. , 2009, European journal of medicinal chemistry.

[54]  B. Kumar,et al.  Preparation and reactions of sugar azides with alkynes: synthesis of sugar triazoles as antitubercular agents. , 2008, Carbohydrate research.

[55]  S. Rollas,,et al.  Synthesis and preliminary anticancer activity of new 1,4-dihydro-3-(3-hydroxy-2-naphthyl)-4-substituted-5H-1,2,4-triazoline-5-thiones. , 2002, Farmaco.

[56]  Helen P. Kavitha,et al.  Synthesis and Biological Applications of Triazole Derivatives – A Review , 2013 .

[57]  Hugo Gallardo,et al.  Synthesis and evaluation of 1-alkyl-4-phenyl-[1,2,3]-triazole derivatives as antimycobacterial agent , 2007 .

[58]  G. V. Suresh Kumar,et al.  Synthesis of some novel 2-substituted-5-[isopropylthiazole] clubbed 1,2,4-triazole and 1,3,4-oxadiazoles as potential antimicrobial and antitubercular agents. , 2010, European journal of medicinal chemistry.

[59]  Vanaja Kumar,et al.  Synthesis of quinoline coupled [1,2,3]-triazoles as a promising class of anti-tuberculosis agents. , 2011, Carbohydrate research.

[60]  M. Spigelman,et al.  Challenges in tuberculosis drug research and development , 2007, Nature Medicine.

[61]  M. Rajan,et al.  Synthesis and preliminary biological evaluation of novel N-(3-aryl-1,2,4-triazol-5-yl) cinnamamide derivatives as potential antimycobacterial agents: an operational Topliss Tree approach. , 2011, Bioorganic & medicinal chemistry letters.

[62]  P. Yogeeswari,et al.  Rational design, synthesis and antitubercular evaluation of novel 2-(trifluoromethyl)phenothiazine-[1,2,3]triazole hybrids. , 2014, Bioorganic & medicinal chemistry letters.

[63]  Beena,et al.  Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and in vivo antimycobacterial activity evaluation. , 2014, European journal of medicinal chemistry.

[64]  Sang-Nae Cho,et al.  Design and synthesis of 1H-1,2,3-triazoles derived from econazole as antitubercular agents. , 2012, Bioorganic & medicinal chemistry letters.