Recent advancements in the development of anti-tuberculosis drugs

Chetty, Sarentha; Ramesh, Muthusamy; Singh, Parvesh; Soliman, Mahmoud E. S.

doi:10.1016/j.bmcl.2016.11.084

Cited by 103 publications

(42 citation statements)

References 174 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MtB is a slow-growing or non-replicating pathogen that requires prolonged antibiotic treatments (i.e., ≥6 months), often with multiple drug combinations due to problems with drug-resistance 36–38 . To further compound these problems, currently there is an inadequate antibiotic pipeline for new MtB drugs 37 . With active HPs targeting both rapidly-dividing planktonic and persistent biofilm cells of Gram-positive pathogens, we felt that HPs could demonstrate antibacterial activities against the persistent pathogen, MtB.…”

Section: Resultsmentioning

confidence: 99%

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis

Yang

Abouelhassan

Burch

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Unlike individual, free-floating planktonic bacteria, biofilms are surface-attached communities of slow- or non-replicating bacteria encased within a protective extracellular polymeric matrix enabling persistent bacterial populations to tolerate high concentrations of antimicrobials. Our current antibacterial arsenal is composed of growth-inhibiting agents that target rapidly-dividing planktonic bacteria but not metabolically dormant biofilm cells. We report the first modular synthesis of a library of 20 halogenated phenazines (HP), utilizing the Wohl-Aue reaction, that targets both planktonic and biofilm cells. New HPs, including 6-substituted analogues, demonstrate potent antibacterial activities against MRSA, MRSE and VRE (MIC = 0.003–0.78 µM). HPs bind metal(II) cations and demonstrate interesting activity profiles when co-treated in a panel of metal(II) cations in MIC assays. HP 1 inhibited RNA and protein biosynthesis while not inhibiting DNA biosynthesis using 3H-radiolabeled precursors in macromolecular synthesis inhibition assays against MRSA. New HPs reported here demonstrate potent eradication activities (MBEC = 0.59–9.38 µM) against MRSA, MRSE and VRE biofilms while showing minimal red blood cell lysis or cytotoxicity against HeLa cells. PEG-carbonate HPs 24 and 25 were found to have potent antibacterial activities with significantly improved water solubility. HP small molecules could have a dramatic impact on persistent, biofilm-associated bacterial infection treatments.

show abstract

Section: Resultsmentioning

confidence: 99%

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis

Yang

Abouelhassan

Burch

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Synthetic indole derivatives are recently published as antimalarials and indole carboxamides, in particular, exhibit antitubercular activity . Ethanamides 1 a ‐ f bear side chains consisting of various heterocyclic and carbocyclic rings, which are present in potent antimycobacterials (Table ). The presence of the trifluoromethoxy group, in the para position, was found to exert a positive impact on antibacterial activity and on the metabolic stability of the performing congeners .…”

Section: Figurementioning

confidence: 99%

Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest

et al. 2019

View full text Add to dashboard Cite

The synthesis and preliminary pharmacological evaluation of new indole and adamantane amido derivatives is described. The design was based on the pharmacophoric properties of 4‐{4‐[4‐(trifluoromethoxy)phenoxy]piperidin‐1‐yl), 6‐[4‐(trifluoro methoxy)phenyl]pyridin‐3‐yl and 4‐(trifluoro)phenyl tails, which are present as side chains in the structures of promising drug candidates, currently in clinical tests. These pharmacophores were incorporated into the indole and adamantane scaffolds, respectively. The new derivatives were evaluated for their antimycobacterial potential. The following amides, N‐[2‐(5‐methoxy‐1H‐indol‐3‐yl)ethyl]‐4‐{4‐[4(trifluoromethoxy)phenoxy]piperidin‐1‐yl}benzamide (1 b) and N‐{4‐[4‐(4‐(trifluoromethoxy)phenoxy)piperidin‐1‐yl]benzyl}‐1H‐indolyl‐2‐carboxamide (2 b), are endowed with antitubercular properties, which merit further investigation.

show abstract

“…Streptomycin (Figure ), the first antibiotic widely used for the treatment of TB, exerted an inhibitory effect by preventing the initiation of protein translation (Chetty, Ramesh, Singhpillay, & Soliman, ). Isoniazid and ethionamide interfered with the biosynthesis of mycolic acids found in cell walls by inhibiting the NADH‐dependent enoyl‐acyl carrier protein reductase (Raju et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the proper regimen for MDR‐TB was as long as 6–9 months and required a combination of several drugs (Reddy, Hosamani, & Devarajegowda, ; Saraiva et al, ). Extensively drug‐resistant tuberculosis (XDR‐TB) was similar to MDR‐TB, except that XDR‐TB has an added resistance to second TB drugs such as capreomycin and amikacin or fluoroquinolone antibiotics (Chetty et al, ; Gonçalves et al, ).…”

Section: Introductionmentioning

confidence: 99%

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Wang

et al. 2020

Drug Development Research

View full text Add to dashboard Cite

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease.To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure-activity relationships, and mechanisms of action. K E Y W O R D Santi-TB drug, antitubercular activities, five-membered ring, MDR-TB, tuberculosis

show abstract

Recent advancements in the development of anti-tuberculosis drugs

Cited by 103 publications

References 174 publications

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis

A Highly Potent Class of Halogenated Phenazine Antibacterial and Biofilm-Eradicating Agents Accessed Through a Modular Wohl-Aue Synthesis

Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest

Opportunities and challenges of using five‐membered ring compounds as promising antitubercular agents

Contact Info

Product

Resources

About