Identification and further development of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B

Vintonyak, Viktor V.; Warburg, Karin; Over, Bjӧrn; Hübel, Katja; Rauh, Daniel; Waldmann, Herbert

doi:10.1016/j.tet.2011.04.026

Cited by 49 publications

(25 citation statements)

References 22 publications

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“…Other groups also have successfully identified inhibitors of PtpB: indole derivatives with selectivity indexes up to 100 [16], cyclic hexapeptides from cyanobacterium Tychonema sp. with IC 50 around 8.0 µM [17], an isoxazole with K i value of 0.22 μM [18], selective indolin-2-on-3-spirothiazolidinones with IC 50 values of 35.5 to 1.2 µM [19] and, recently, benzofurans with sub-micromolar inhibitory activity [20]. Based on these evidences, PtpB has emerged as an important target for anti-TB pharmacological intervention and new inhibitors are in high demand [21].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products

et al. 2013

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Protein tyrosine phosphatase B (PtpB) is one of the virulence factors secreted into the host cell by Mycobacterium tuberculosis. PtpB attenuates host immune defenses by interfering with signal transduction pathways in macrophages and, therefore, it is considered a promising target for the development of novel anti-tuberculosis drugs. Here we report the discovery of natural compound inhibitors of PtpB among an in house library of more than 800 natural substances by means of a multidisciplinary approach, mixing in silico screening with enzymatic and kinetics studies and MS assays. Six natural compounds proved to inhibit PtpB at low micromolar concentrations (< 30 µM) with Kuwanol E being the most potent with K i = 1.6 ± 0.1 µM. To the best of our knowledge, Kuwanol E is the most potent natural compound PtpB inhibitor reported so far, as well as it is the first non-peptidic PtpB inhibitor discovered from natural sources. Compounds herein identified may inspire the design of novel specific PtpB inhibitors.

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Section: Introductionmentioning

confidence: 99%

Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products

et al. 2013

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“…A series of compounds exemplified by general structure 293 were synthesized and it was observed that small structural modifications and configuration of the spiro‐center leads to increase in solubility and cell permeability and promising inhibition of MptpB up to IC 50 of 1.1 μM. These compounds also showed selectivity over panel of other protein tyrosine phosphatase, such as MptpA, PTP1B, PTPN2, and VHR . Aridoss et al.…”

Section: Thiazolidinonesmentioning

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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“…1H-indole-2,3-dione [1] and thiazolidine [2] are the privileged scaffolds in the modern medicinal chemistry that have a broad spectrum of the biological activity including antimicrobial [7], antioxidant [4], antimycobacterial [5], antidepressant [6], anticonvulsant [6] effects. A considerable interest has been focused on the anticancer activity of isatin [7] and thiazolidine [8,9] derivatives.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Activity of Isatin, Oxadiazole and 4-Thiazolidinone Based Conjugates

Lelyukh¹,

Havrylyuk²,

Lesyk³

2015

ChChT

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Abstract.Following the N-alkylation reaction of starting 2-chloro-N-(5-aryl-1,3,4-oxadiazol-2-yl)-acetamides 1a-c with 2,4-thiazolidinedione or 5-sudstituted isatins the corresponding non-condensed oxadiazole derivatives with thiazolidine 2a-c or isatin 4a-h fragments were synthesized. The obtained compounds have been used in Knoevenagel condensation with 5R-isatin (for 2a-c) or 4-thiazolidinone derivatives (for 4a-h) for synthesis of the appropriate 5-ylidenederivatives 3a-g, 5a-k and 6a-d. Anticancer activity of eight synthesized compounds was evaluated toward 60 human tumor cell lines panel in National Cancer Institute.

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Identification and further development of thiazolidinones spiro-fused to indolin-2-ones as potent and selective inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase B

Cited by 49 publications

References 22 publications

Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products

Discovery of Mycobacterium tuberculosis Protein Tyrosine Phosphatase B (PtpB) Inhibitors from Natural Products

New structural classes of antituberculosis agents

Synthesis and Anticancer Activity of Isatin, Oxadiazole and 4-Thiazolidinone Based Conjugates

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