Exploring Azatidinone Moiety: An Insight into its Anti-tubercular Potency

Abstract

TB is becoming a worldwide problem and it was declared since 1993 by the World Health Organization (WHO), a global health emergency. The current problem of tuberculosis therapy is the emergence of multi-drug resistant (MDR) strains, caused by the improper use of antibiotics in chemotherapy of TB patients. Azatidinones, a β-lactam cyclic amide with four atoms in a ring, has been considered as a magic moiety (wonder nucleus) which possesses almost all types of biological activities. This diversity in the biological response profile has attracted the attention of many researchers to explore this skeleton to its multiple potential against several activities. Present article is sincere attempt to review chemistry, method of synthesis of azatidinones and to study azatidinones synthesized in last few years which have shown potent antitubercular activity.

Key words

antitubercular activity - azatidinones - β-lactam cyclic amide - tuberculosis (TB) - multi-drug resistant - antitubercular drugs

Publication History

Received: 27 December 2020

Accepted: 12 April 2021

Article published online:
25 May 2021

• References

• 1 MVN DeSouza. Current status and future prospects for new therapies for pulmonary tuberculosis. Curr Opin Pulm Med 2006; 12: 167-171
• 2 De Souza MVN. Promising drugs against tuberculosis in recent past. Anti-Infect. Drug Discovery 2006; 1: 3344-3349
• 3 Swamy BN, Suma TK, Rao GV. et al. Synthesis of isonicotinoylhydrazones from anacardic acid and their in-vitro activity against Mycobacterium smegmatis. Eur J Med Chem 2007; 42: 420-424
• 4 Janin YL. Antituberculosis drugs: Ten years of research. Bioorg Med Chem 2007; 15: 2479-2513
• 5 Scior T, Garces. Eisele SJ. Isoniazid is not a lead compound for its pyridyl ring derivatives, isonicotinoyl amides, hydrazides, and hydrazones: A critical review. Curr Med Chem 2006; 13: 2205-2219
• 6 Ballell L, Field RA, Duncan K. et al. New small-molecule synthetic antimycobacterials. Antimicrob Agents and Chemotherapy 2005; 49: 2153-2163
• 7 Sriram D, Bal TR, Yogeeswari P. Newer aminopyrimidinimino isatin analogues as non-nucleoside HIV-1 reverse transcriptase inhibitors for HIV and other opportunistic infections of AIDS: Design, synthesis and biological evaluation. Il Farmaco 2005; 60: 377-384
• 8 Berry M, Kon OM. Multidrug and extensively drug-resistant tuberculosis: an emerging threat. Eur Respir Rev 2009; 18: 195-197
• 9 Szekely R, Waczek F, Szabadkai I. et al A novel drug discovery concept for tuberculosis: Inhibition of bacterial and host cell signaling. Immunology Letters 2008; 116: 225-231
• 10 Somu RV, Boshoff H, Qiao C. et al. Rationally designed nucleoside antibiotics that inhibit siderophore biosynthesis of mycobacterium tuberculosis . J Med Chem 2006; 49: 31-34
• 11 Sacchettini JC, Rubin EJ, Freundlich JS. Drugs versus bugs: In pursuit of the persistent predator Mycobacterium tuberculosis . Nat Rev Microbiol 2008; 6: 41-52
• 12 Snider JDE, Castro KG. The global threat of drug-resistant tuberculosis. Eng J Med 1998; 338: 1689-1690
• 13 Global Tuberculosis Control: Surveillanc e, Planning, Financing WHO Report 2008; 51-54
• 14 Ruiz SMJ, Alcala L, Martinez L. et al In-vitro activities of six fluoroquinolones against 250 clinical isolates of Mycobacterium tuberculosis susceptible or resistant to first-line antituberculosis drugs. Antimicrob Agents Chemother 2000; 44: 2567-2568
• 15 Smith CV, Sharma V, Sacchettini JC. et al TB drug discovery: Addressing issues of persistence and resistance. Tuberculosis 2004; 84: 45-55
• 16 Sullivan EA, Kreiswirth BN, Palumbo L. Emergence of fluoroquinolone-resistant tuberculosis in New York City. Lancet 1995; 345: 1148-1150
• 17 Teodori E, Dei S, Scapecchi S. et al. The medicinal chemistry of multidrug resistance (MDR) reversing drugs. Il Farmaco 2000; 57: 385-415
• 18 Russell DG. Mycobacterium tuberculosis: here today, and here tomorrow. Nat Rev Mol Cell Biol 2001; 2: 569-577
• 19 Omar A, Ahmed MA. Synthesis of some new 3H-quinazolin-4-one derivatives as potential antitubercular agents. World Appl Sci. Journal 2008; 5: 94-99
• 20 O'Brien RJ, Nunn PP. The need for new drugs against tuberculosis. Obstacles, opportunities, and next steps. Am J Respir Crit Care Med 2001; 163: 1055-1058
• 21 Glickman SW, Rasiel EB, Hamilton CD. et al. A portfolio model of drug development for tuberculosis. Science 2006; 311: 1246-1247
• 22 Tomioka H. Prospects for development of new antituberculous drugs. Kekkaku 2002; 77: 573-584
• 23 Duncan K, Barry CE. Prospects for new antitubercular drugs. Curr. Opin Microbiol. 2004; 7: 460-465
• 24 Manhas MS, Bose AK. Synthesis of penicillin and cephalosporin C and Analogs. Marcel Dekker; New York: 1969: 13
• 25 Mukerjee AK, Singh AK. β-lactams: Retrospect and prospect. Tetrahedrons 1978; 34: 1731
• 26 Morin RB, Gorman M. Chemistry and Biology of b-Lactam Antibiotics. Academic; New York: 1982: 1-3
• 27 De Kimpe N. Comprehensive Heterocyclic Chemistry-II; Katritzky, A. R., Rees, C. W., Scriven, E. V. F., Padwa, A., Eds. Pergamon; Oxford: 1996. Vol. 1B. 507
• 28 Singh GS, Singh T, Lakhan R. Synthesis ¹³C-NMR and anticonvulsant activity of new isatin-based spiroazetidinones. Indian J. Chem. 1997; 36(B) 951
• 29 Barrett AGM, Baugh SPD, Gibson VC. et al. Highly functionalised monocyclic and bicyclic β-lactams via alkene metathesis. Chem. Commun. 1997; 155
• 30 Shindo M, Oya S, Sato Y. et al. Cycloaddition of lithium ynolate to imines: Synthesis of 3,4-disubstituted β-lactams. Heterocycles 1998; 49: 113
• 31 De Risi C, Pollini GP, Veroneze AC. et al. A new simple route for the synthesis of (±)-2-azetidinones starting from β-enaminoketoesters. Tetrahedron Lett 1999; 40: 6995
• 32 Naskar D, Roy S. Synthesis of a-bromo-lactam via a novel catalytic Hunsdiecker like protocol. J. Chem. Soc. Perkin Trans 1999; 1: 2435
• 33 Silverstein RM, Bassler GC, Morrill TC. Spectrometric Identification of Organic Compounds. 4th Ed. John Wiley and Sons; New York, U.S.A: 1981: 117-127
• 34 Pavia DL, Lampman GM, Kriz GS. Introduction to Spectroscopy: A Guide for Students of Organic Chemistry. Saunders College Publishing; Orlando, Florida, U.S.A.: 1979
• 35 Staudinger H, Enke F. Die Ketene, Stuttgart,F publictn, Germany. 1912
• 36 Joyeau R, Molines H, Labia R. et al. N-aryl 3-halogenated azetidin-2-ones and benzocarbacephems, inhibitors of beta-lactamases. J. Med. Chem. 1988; 31: 370
• 37 Manhas MS, Chawla HPS, Amins G. et al. Studies on Lactams. Synthesis. 1977; 6: 407
• 38 Bose AK, Banik BK, Manhas MS. Stereocontrol of β-lactam formation using microwave irradiation. Tetrahedron Lett 1995; 36: 213
• 39 Bose AK, Chiang YH, Manhas MS. One step synthesis of α-amido-β-lactams. Tetrahedron Lett 1973; 14: 2503-2506
• 40 Patel P, Korgaokar S, Parikh K. et al. Synthesis and biological activity of 2 azetidinones, sulphonamides, arylamides and thiourea derivatives. IJC,38(B) 1999; 696-700
• 41 Kaythara P, Upadhayay T, Doshi R. et al. Synthesis of some 2-azetidinones as a potential anti- tubercular agents. Indian Journal of Heterocyclic Chemistry 2000; 10: 09-12
• 42 Khyati PA, Oza PS, Bhatt SB. et al. Synthesis of some new 2 azetidinones as potential anti tubercular agents. Indian Journal of Chemistry. 2000; 39(B) 716-718
• 43 Thakar KM, Kachhadia VV, Joshi HS. Synthesis of 4- thiazolidinones and 2-azetidinones bearing benzo (b) thiophene nucleus as potential antitubercular and antimicrobial agents. Indian Journal of Chemistry. 2003; 42(B) 1544-1547
• 44 Patel RB, Desai PS, Desai KR. et al. Synthesis of pyrimidine based thiazolidinones and azetidinones : antimicrobial and antitubercular agents. Indian Journal of Chemistry. 2006; 45(B) 773-778
• 45 Basawaraj R, Amith L, Vijay T. et al. Synthesis and Antitubercular Activities of Azetidinone and Thiazolidinone Derivatives from 5-Chloro-3-Methylbenzofuran. International Journal of ChemTech Research 2010; 2: 1764-1770
• 46 Dighe RD, Rohom SS, Deshpande MM. et al. Microwave assisted synthesis and evaluation of isatinyl thiazole derivatives as anti-Mycobacterium tuberculosis agents and dTDP-rhamnose inhibitors. IJRPBS 2011; 2: 776
• 47 Ilango K, Arunkumar S. Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Trihydroxy Benzamido Azetidin-2-one Derivatives. Tropical Journal of Pharmaceutical Research 2011; 10: 219-229
• 48 Rajasekaran M, Periasamy. Venkatesan S. Synthesis, characterization and biological activity of some novel azetidinones. Journal of Developmental Biology and Tissue Engineering 2010; 2: 5-13
• 49 Ayarivan,Puratchikody.; Ramalakshmi,Natarajan.;Mohanapriya,Jayapal.;Mukesh Doble. Synthesis, In-vitro Antitubercular Activity and 3D-QSAR of Novel Quinoxaline Derivatives. Chem Biol Drug Des 2011; 78: 988-999
• 50 Himaja M. Karigar,Asif. Synthesis of novel azetidinones derivatives as anti tubercular agents. Letters in Drug Design and Discovery 2012; 9: 611-617
• 51 Jaya P, Preethi K, Bindu Sree K. et al. Synthesis, Characterization and Its Biological Evaluation of Some Novel 4-Thiazolidinone and 2-Azetidinone Derivatives. Asian. J. Pharm. Res 2012; 2: 63-70
• 52 Mohite PB, Bhaskar VH. In-vitro evaluation of tetrazoles as a novel class of anti-mycobacterium tuberculosis agents. Advanced Pharmaceutical Bulletin 2012; 2: 31-36
• 53 Ritu Sharma, Pushkal Samadhiya, Srivastava S.D. et al. Synthesis and pharmaceutical importance of 2-azetidinone derivatives of phenothiazine. J. Chem. Sci. 2012; 124: 633-637
• 54 Pathak RB, Chovatia PT, Parekh HH. Synthesis, antitubercular and antimicrobial evaluation of 3-(4-chlorophenyl)-4-substituted pyrazole derivatives. Bioorg Med Chem Lett 2012; 22: 5129-5133
• 55 Myangar KN, Akhaja TN, Naik DR. et al. Synthesis of novel azetidinyl-3-( isonicotinamide-yl)-6-iodo-quinazolin-4-ones as antimicrobial and antitubercular agents .IJPSN 2012; 5: 1735
• 56 Pushkal Samadhiya, Ritu Sharma, Santosh K, Srivastava A, Savitri DSrivastava. Synthesis of 2-oxoazetidine derivatives of 2-aminothiazole and their biological activity. J. Serb. Chem. Soc 2012; 77: 599-605
• 57 Saundane AR, Walmik P. Synthesis, Antioxidant, Antimicrobial, Antimycobacterial, and Cytotoxic Activities of Azetidinone and Thiazolidinone Moieties Linked to Indole Nucleus. Journal of Chemistry 2013; 1-9
• 58 Patel NB, Pathak KK. Pyridoquinolones containing azetidinones: synthesis and their biological evaluation. Med chem. Res. 2012; 21: 2044-2055
• 59 Joshi SD, More UA, Parkale D. et al Design, synthesis of quinolinyl Schiff bases and azetidinones as enoyl ACP-reductase inhibitors. Med Chem Res 24 2015; 3892-391
• 60 Thomas B, Harindran J. Design, synthesis and evaluation of antitubercular activity of amino azetidinones from isoniazid. Int J Pharm Sci Res 2016; 7: 2795-04
• 61 Sarkar S. Design, Synthesis, and evaluation of antitubercular activity of novel benzothiazole-containing an azetidinone ring. Istanbul J Pharm 2018; 48: 28-31
• 62 Dadlani Vedika, Tripathi Pushpendra, Somani Rakesh. Design, molecular docking and in-silico analysis of novel thiadiazole-azetidinone hybrids as potential antitubercular agents. Int J of Resh in Pharmaceutical Sciences 2019; 10: 3694-3703
• 63 Suresh SK, Arun S, Shrinivas DJ, Siddappa A.Patil. Design. synthesis, molecular docking and biological activity studies of novel coumarino-azetidinones, J of Molecular Structure 2021; 1231: 130016
• 64 Vaijinath AV, Anand RS, Rajkumar SM. et al. Synthesis, biological evaluation and docking studies of some new indolyl-pyridine containing thiazolidinone and azetidinone analogs. Polycyclic aromatic compounds 2020;
• 65 Nimbalkar UD, Seijas JA, Borkute R. Ultrasound Assisted Synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold. Molecules 2018; 23: 1945.