Heterocyclic Isosters of Antimycobacterial Salicylanilides.

Matyk, Josef; Waisser, Karel; Drazkova, Katerina; Kuneš, Jiřı́; Klimešová, Věra; Palát, Karel; Kaustová, Jarmila

doi:10.1002/chin.200539076

Cited by 3 publications

(3 citation statements)

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“…9 Substituted heterocyclic analogues of salicylanilides have shown promising antimycobacterial activity, thus representing potential antituberculotics. 10 Additionally, substituted benzanilides can act as potassium channel activators with some derivatives characterized as potent smooth muscle relaxants. 11 Steffen and coauthors investigated the activity of modified salicylanilides as cellpermeable inhibitors of poly(ADP-ribose) glycohydrolase that can modulate both the cell recovery or cell death depending on the level of the exerted DNA damage.…”

Section: ■ Introductionmentioning

confidence: 99%

Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study

Perin

Roškarić

Sović

et al. 2018

Chem. Res. Toxicol.

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We prepared a range of N-arylbenzamides with a variable number of methoxy and hydroxy groups, bearing either amino or amino-protonated moieties, and used DPPH and FRAP assays to evaluate their antioxidant capacity. Most of the systems exhibit improved antioxidative properties relative to the reference BHT molecule in both assays. Combining results from both sets of experiments, the most promising antioxidative potential was displayed by the trihydroxy derivative 26, which we propose as a lead compound for a further optimization of the benzamide scaffold. Computational analysis helped in interpreting the observed trends and demonstrated that protonated systems are better antioxidants than their neutral counterparts, while underlying the positive influence of the electron-donating methoxy group on the antioxidant properties, thus confirming the experiments. It also revealed that the introduction of the hydroxy groups shifts the reactivity from both amide and amine groups toward this moiety and additionally enhances antioxidative features. This is particularly evident in 26H, which owes its pronounced reactivity to the stabilizing [O···H-O] hydrogen bonding between the created phenoxyl radical and the two neighboring hydroxy groups. We demonstrated that its antioxidative activities are more favorable than those for analogous trihydroxy derivatives without the N-phenyl group or without the amide moiety, which strongly justifies the employed strategy in utilizing bisphenylamides in designing potent antioxidants.

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Section: ■ Introductionmentioning

confidence: 99%

Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study

Perin

Roškarić

Sović

et al. 2018

Chem. Res. Toxicol.

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“…It is likely that the survival of M tuberculosis against the macrophage phagocytosis relies not only on a thick cell wall but also on many o f the mycobacterial kinases (or phospha tases) which disrupt the host-cell defence mechanism against such parasitism [281], Concerning the specific inhibition of signal transduction system m mycobacteria, a series o f an timycobactenal salicylanilides (52) were recently reported [282,283], Inhibition o f this regulatory system probably remains a worthy research subject since regulation of this type is involved in the virulence of M tuberculosis in mice [284] Eleven putative eukaryotic-like protein senne-threomne kinases (PknA to L) involved in signal transduction were identified in M tuberculosis H37Rv genome [6,[285][286][287]. Moreover, the 'generic' kinase inhibitor (53) [288] as well as other more complex compounds [289] were shown to inhibit the growth of some mycobacteria Protein kinase PknG does not have a transmembrane domain and could be a secreted Fig.…”

Section: Signal Transduction Inhibitorsmentioning

confidence: 99%

New Frontiers in the Therapy of Tuberculosis: Fighting with the Global Menace

Chhabria

Jani²,

Patel

2009

MRMC

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Tuberculosis has remained an enemy of humankind since its inception. It has affected all facets of human life and remained leading cause of mortality and morbidity despite of availability of effective chemotherapy and BCG vaccine in 21st century. This has exposed the frailties of the current drug armamentarium. No new drug is available acting through novel mechanism of action for last 40 years. This has culminated into resistant strain of TB, MDR-TB and XDR-TB. Concomitant occurrence of TB and HIV presents a lethal combination. The availability of the M. tuberculosis genome sequence and mycobacterial genetic tools, such as transposon mutagenesis, gene knockout and gene transfer, greatly facilitate target identification. This review provides a comprehensive literature compilation on the present research paradigm of anti-TB drug discovery including advances in the new structural classes analogs reported in last decade.

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“…Histidine kinase is the focus for the specific inhibition of two component signal transduction system in mycobacteria (95)(96)(97)(98). Based on this signal transduction system, a series of antimycobacterial salicylanilides and related compounds have been reported (99)(100)(101)(102). Inhibition of this type of regulation has been involved in the virulence of M. tuberculosis in mice (103).…”

Section: 24-benzothiadiazinesmentioning

confidence: 99%

Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds

et al. 2008

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Development of new chemotherapeutic drugs is the need of the hour to improve tuberculosis control, particularly in the developing world. In the last fourty years no new compound has been brought to the market for the treatment of tuberculosis. However, in recent years there is an enhanced activity in the research and development of new drugs for TB. Some compounds are presently in clinical development, while others are being investigated pre-clinically in an attempt to explore new molecules for the target based treatment of TB. Simultaneously some new targets are being identified and validated for their practical usefulness. Structures based on thiolactomycin could have considerable potential in the development of target based anti-TB agents. The present review provides an overview of the drugs that are being clinically used and the compounds that are in advanced stages of clinical as well as preclinical studies. We have also attempted to highlight the efforts that are being made in the development of new molecules based on thiolactomycin as lead compound, including studies from this laboratory.

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Heterocyclic Isosters of Antimycobacterial Salicylanilides.

Cited by 3 publications

References 1 publication

Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study

Amino-Substituted Benzamide Derivatives as Promising Antioxidant Agents: A Combined Experimental and Computational Study

New Frontiers in the Therapy of Tuberculosis: Fighting with the Global Menace

Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds

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