Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and in vivo antimycobacterial activity evaluation

Kumar, Deepak; Beena,; Khare, Garima; Kidwai, Saqib; Tyagi, Anil K.; Singh, Ramandeep; Rawat, Diwan S.

doi:10.1016/j.ejmech.2014.05.005

Cited by 88 publications

(35 citation statements)

References 56 publications

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“…Compound ( 12 ) was the most active derivative (MIC 99 = 0.195–0.39 μ m ), being twofold more effective than isoniazid (INH, MIC 99 = 0.39 μ m ) and also tested for its in vivo activity, which evidenced mild activity in case of lung as well as spleen. The influence of the compound on the replication of the pathogen was far superior in the case of spleen compared to the influence on the lung . Menendez and coworkers described synthesis of 1,2,3‐triazoles bearing alkyl and aryl/alkyl chain using click chemistry and examined their anti‐TB activity against MTB H 37 Rv strain.…”

Section: 23‐triazole Derivatives For Treatment Of Tuberculosismentioning

confidence: 99%

Triazole: A Promising Antitubercular Agent

et al. 2015

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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.

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Section: 23‐triazole Derivatives For Treatment Of Tuberculosismentioning

confidence: 99%

Triazole: A Promising Antitubercular Agent

et al. 2015

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“…The compounds exhibited MIC values ranging from 0.195 to 1.56 μM. Compound 330 , the most effective derivative (MIC 99 = 0.195 μM) was twofold more potent than isoniazid (MIC = 0.39 μM) and displayed mild activity in lung and spleen, in vivo . Menendez and co‐workers disclosed that derivatives 331 and 332 modified at the phenyl ring exhibited MIC values of 0.50 and 0.25 μg/mL, respectively, against M. tuberculosis H37Rv, and targets InhA enzyme (Fig.…”

Section: Triazolesmentioning

confidence: 98%

“…Thiosemicarbazone group containing compounds are known for their antimycobacterial activity. Thiacetazone is a commercially available thiosemicarbazone class of compound widely used as a second-line drug for the treatment of 283 Menendez and co-workers disclosed that derivatives 331 and 332 modified at the phenyl ring exhibited MIC values of 0.50 and 0.25 g/mL, respectively, against M.…”

Section: Thiosemicarbazonesmentioning

confidence: 99%

New structural classes of antituberculosis agents

Kumar

Patel

Jain

2017

Medicinal Research Reviews

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Tuberculosis (TB), one of the deadliest diseases is shattering the health and socioeconomic status of the society. The emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains has provided unprecedented lethal character to TB. The development of MDR and XDR strains of TB results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. Because of the development of rapid resistance by Mycobacterium tuberculosis, researchers are confronted with serious challenges in combating TB. For instance, the need for potency and specificity in therapeutic agents approaching clinics, and the increasing demand of low toxicity due to long duration of treatment. Recently, it is proposed that such challenges could be addressed by a shift from contemporary or known classes of drugs to new scaffold-containing or entirely new structural classes of drugs that possibly act on the previously unknown targets, resulting in possibly less instances of resistance development. The exploitation of advances made in the biology of TB in the last and present decades have created opportunities to discover a large number of new structural classes that specifically targets TB by molecular mechanism of action(s) unknown earlier. We have earlier reviewed new structural classes of anti-TB agents up to year 2005. This review covers literature reports of the subsequent 10 years on the discovery of new structural classes of synthetic anti-TB agents. Due to the availability of large number of research reports, we have divided new compounds in 38 structural classes, 368 structures, and 307 references.

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“…Adverse side effects caused by drug therapy may incur substantial additional costs due to outpatient visits, additional tests and, in more serious cases, hospitalisation. Second-line agents often have more severe effects, are less effective, have worse toxicity profiles and are more expensive (Kumar et al 2014a;Yee et al 2003). The treatment duration of second-line agents is often prolonged by 2 years (Kumar et al 2014a), adding additional challenges to patient compliance and resulting in a high risk of treatment failure and relapse (Yee et al 2003).…”

Section: Introductionmentioning

confidence: 99%

“…This triazole scaffold possesses hydrogen bonding capability, moderate dipole character, rigidity and stability under in vivo conditions that all together are responsible for the enhanced biological properties of compounds containing that scaffold (Zhang et al 2017). Interestingly, some triazolecontaining compounds and the mainstay anti-TB drug, INH, share a similar mechanism of action as they inhibit microbial cell wall synthesis by blocking lipid biosynthesis (Kumar et al 2014a;Zhang et al 2017), presumably by targeting the enoyl-acyl carrier protein (PDB ID: 1ZID) that is essential for the fatty acid (mycolic acids) synthase system (FAS-II) in mycobacterial cells (Rozwarski et al 1998). Drugs currently in the market that possess the 1,2,3-triazole moiety include cefatrizine and tazobactam (antibiotics) (Ali et al 2017;Zhang et al 2017), TSAO (anti-HIV) (Zhang et al 2017), and carboxyamidotriazole (CAI) (anticancer) ( Fig.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

Smit

Seldon²,

Aucamp

et al. 2019

Med Chem Res

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The increasing prevalence of multidrug-resistant strains of Mycobacterium tuberculosis (Mtb), the pathogen of human tuberculosis (TB), serves as a strong incentive for the discovery and development of new agents for the treatment of this plight. In search for such drugs, we investigated a series of benzyltriazole derivatives. We herein report the design, synthesis and biological activity of disubstituted benzyltriazoles against the human virulent H37Rv strain of Mtb as well as the toxicity on human embryonic kidney (HEK-293) cells. The derivative 21 featuring trifluoromethyl substituent in para position on the phenyl ring and n-butyl chain in position 4 on the triazole ring was the most active with MIC 90 and MIC 99 values of 1.73 and 3.2 µM, respectively, in the albumin-free medium. It also displays high selectivity towards bacteria growth inhibition (SI > 58), thus stands as a better hit for further investigation, including lead optimization, DMPK parameters determination and assessment of its activity in animal models.

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Synthesis of novel 1,2,3-triazole derivatives of isoniazid and their in vitro and in vivo antimycobacterial activity evaluation

Cited by 88 publications

References 56 publications

Triazole: A Promising Antitubercular Agent

Triazole: A Promising Antitubercular Agent

New structural classes of antituberculosis agents

Synthesis and antimycobacterial activity of disubstituted benzyltriazoles

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