A novel molecule with notable activity against multi-drug resistant tuberculosis

Nair, Vasu; Okello, Maurice; Mangu, Naveen K.; Seo, Byung; Gund, Machhindra

doi:10.1016/j.bmcl.2015.01.050

Cited by 7 publications

(7 citation statements)

References 27 publications

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“…Streptomycin was used as a standard anti-MTB drug, but its MIC was not reported. The in vitro cytotoxicity of Compound 20 was evaluated in uninfected macrophages, and a relatively low percentage of macrophage viability inhibition was found (>85%) [101].…”

Section: Mtb Strainmentioning

confidence: 99%

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens

et al. 2023

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The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient’s immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

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Section: Mtb Strainmentioning

confidence: 99%

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens

et al. 2023

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“…reported that compound 366 (earlier known to be a promising anti‐HIV integrase inhibitor) display impressive activity (MIC = 1.56 μg/mL) against MDR‐TB strain. Compound 366 also showed low cytotoxicity and possessed favorable metabolic profile against human cytochrome P450 and UGT isoenzyme, and when tested in combination with PA‐824, showed enhancement in activity (MIC = 0.195 μg/mL) . From the high‐throughput biochemical and NMR‐based fragment screening, Panda et al.…”

Section: Miscellaneous Structural Classesmentioning

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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“…Among these compounds, several heterocycles and scaffolds are contemplated, including benzo[ d ]isoxazole ( 39 ) [65], benzo[ b ]thiophenes ( 40 ) [66], disubstituted piperazine ( 41 ) [67], and benzoxazole ( 42 ) [68] (Figure 13). …”

Section: Antituberculosis Compoundsmentioning

confidence: 99%

“…Indeed, the scientific literature presents several works involving only the synthesis and phenotypic screening of compounds against MDR strains accompanied by in silico studies. Among these compounds, several heterocycles and scaffolds are contemplated, including benzo[ d ]isoxazole ( 39 ) [ 65 ], benzo[ b ]thiophenes ( 40 ) [ 66 ], disubstituted piperazine ( 41 ) [ 67 ], and benzoxazole ( 42 ) [ 68 ] ( Figure 13 ).…”

Section: Antituberculosis Compoundsmentioning

confidence: 99%

“…In vitro microsome stability study exhibited a T 1/2 of 14.4 h and low inhibition of two isoforms of cytochrome P450, namely CYP3A4 and CYP2D6. Moreover, the authors suggested that compound ( 41 ) might act through inhibition of mycobacterial DNA-dependent RNA polymerase [ 67 ]. The benzoxazole derivative ( 42 ) also showed to be a promising antituberculosis agent.…”

Section: Antituberculosis Compoundsmentioning

confidence: 99%

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Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds

2017

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Tuberculosis (TB), a disease caused mainly by the Mycobacterium tuberculosis (Mtb), is according to the World Health Organization (WHO) the infectious disease responsible for the highest number of deaths worldwide. The increased number of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. The scenario of drug discovery becomes alarming when it is considered that the number of new drugs does not increase proportionally to the emergence of drug resistance. In this review, we will demonstrate the current advances in antitubercular drug discovery, focusing on the research of compounds with potent antituberculosis activity against MDR-TB strains. Herein, active compounds against MDR-TB with minimum inhibitory concentrations (MICs) less than 11 µM and low toxicity published in the last 4 years in the databases PubMed, Web of Science and Scopus will be presented and discussed.

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A novel molecule with notable activity against multi-drug resistant tuberculosis

Cited by 7 publications

References 27 publications

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens

New structural classes of antituberculosis agents

Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds

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