New Small-Molecule Synthetic Antimycobacterials

Ballell, Lluís; Field, Robert A.; Duncan, Ken; Young, Robert J.

doi:10.1128/aac.49.6.2153-2163.2005

Cited by 166 publications

(100 citation statements)

References 98 publications

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“…Hbond donor, flexibility and C logP are part of "Lipinski rule of 5" which describes the drug likeliness property and they play a major role in designing anti-tubercular drugs. 23) Moment of inertia is also an indication of the size and shape of the molecule.…”

Section: Resultsmentioning

confidence: 99%

QSAR Studies on Chalcones and Flavonoids as Anti-tuberculosis Agents Using Genetic Function Approximation (GFA) Method

2007

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Tuberculosis is an infection caused by Mycobacterium tuberculosis, which commonly affects the respiratory tract, i.e. lungs.1) It is termed as "a global health emergency" by world health organization (WHO) in 1993 as it affects 1.7 billion people per year, that is equal to one-third of the entire world population. The first line of drugs used in the treatment of tuberculosis (TB) is a combination of isoniazid, rifampicin, pyrazinamide and ethambutol. The high concentration of lipids in the cell wall of M. tuberculosis has been attributed to its resistant to antibiotics. The lipid fraction of cell wall consists of three major components mycolic acids, cord factor and wax-D. Isoniazid is known to inhibit the synthesis of mycolic acid. Ethambutol is known to inhibit the incorporation of mycolic acid into the cell wall. Rifampicin acts by binding to DNA-dependent RNA polymerase and inhibits initiation of RNA synthesis. Pyrazinoic acid, the active form of pyrazinamide, is reported by Zhang Y., et al. to inhibit M. tuberculosis membrane transport function and disrupt membrane energetics.2) It is expected that the disease can be completely eliminated with the help of combination therapy, but these hopes were dashed with the advent of drug resistant strains. The development of drug resistant strains is due to point mutations in the bacterial chromosome, resulting in changes in the antibiotic target that renders the strain no longer susceptible to the drug.Thus the increasing clinical importance of tuberculosis has lent additional urgency to researchers to identify new and effective antimycobacterial compounds. Literature survey reveals that chalcones, flavones and flavanones possess antiinflammatory, 3) anticancer, 4) antileishmanial, 5) antimalarial, 6) antimicrobial and antioxidant 7) activities. It is reported that the chalcones and their derivatives are more effective against Gram-positive bacteria than against Gram-negative bacteria. 8)But it is interesting to note that they are also effective against this acid-fast bacillus which is neither Gram-positive nor negative. These compounds show very good activity against H37Rv strain. Understanding the effect of structural features on the activity would help the researchers to design new molecules that may exhibit higher activity. Quantitative structure activity relationship (QSAR) approach is better for designing new drugs when the target is not known or if there are multiple targets.QSAR studies on heterocyclic analogues of salicylanilides performed through the combination of Free-Wilson and Hansch approach explains the influences of electronic and hydrophobic properties.9) Gupta M. K., et al. have observed that topological descriptors are correlated with the antimycobacterial activity of nitro/acetamido alkenol and chloro/amino alkenol derivatives.10) 3D-QSAR uses three-dimensional properties of the molecules (particularly steric and electrostatic factors) and correlates these descriptors with the biological activity. 3D-QSAR studies carried out by Shagufta, et al. o...

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Section: Resultsmentioning

confidence: 99%

QSAR Studies on Chalcones and Flavonoids as Anti-tuberculosis Agents Using Genetic Function Approximation (GFA) Method

2007

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“…Parameters applied to assess the "quality" of antimycobacterial molecules consider a new compound to be bioactive if it possesses an MIC a 6.25 lg/mL and is endowed with an attractive physicochemical profile (compatible to the "Lipinski rule of 5") [18].…”

Section: Resultsmentioning

confidence: 99%

Novel Nitrofurazone Derivatives Endowed with Antimicrobial Activity

Brondani

Caetano

Moreira

et al. 2008

Archiv der Pharmazie

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“…The 13 C-NMR signal of the S-CH 2 group can be observed at 32.6 to 34.5 ppm, the signal of the O-CH 2 esters can be found at 61.5 to 61.6 ppm, the signal of the CH 3 ; bending vibration of the NH 2 group of hydrazides will be seen in the region 1617 to 1629 cm -1 .…”

Section: Chemistrymentioning

confidence: 93%

“…Thiols 3 were prepared by heating appropriate benzyl halides with thiourea in ethanol, and the resulting S-alkylisothiouronium salts were further hydrolyzed by an aqueous solution of sodium hydroxide. The treatment of 2 with various benzylthiols 3 was carried out in dioxane and iPr 2 NEt in the presence of catalyst Pd 2 (dba) 3 and Xantphos at reflux. The process required 9 to 12 h depending on the alkylating agent and furnished products 4 in 32 to 68% yields.…”

Section: Chemistrymentioning

confidence: 99%

Preparation and in‐vitro Evaluation of 4‐Benzylsulfanylpyridine‐2‐carbohydrazides as Potential Antituberculosis Agents

Herzigova

Klimešová²,

Palát

et al. 2009

Archiv der Pharmazie

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A set of 4-benzylsulfanylpyridine-2-carbohydrazides was synthesized and evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis, non-tuberculous mycobacteria, and multidrug-resistant M. tuberculosis. The activities expressed as the minimum inhibitory concentration (MIC) fall into a range of 2 to 125 micromol/L, most often 4 to 32 micromol/L. The results revealed that the substituents on the benzyl moiety do not influence the antimycobacterial efficacy. The substances exhibited similar activities against sensitive and resistant strains of M. tuberculosis. Furthermore, compounds show low antiproliferative effect and cytotoxicity.

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New Small-Molecule Synthetic Antimycobacterials

Cited by 166 publications

References 98 publications

QSAR Studies on Chalcones and Flavonoids as Anti-tuberculosis Agents Using Genetic Function Approximation (GFA) Method

QSAR Studies on Chalcones and Flavonoids as Anti-tuberculosis Agents Using Genetic Function Approximation (GFA) Method

Novel Nitrofurazone Derivatives Endowed with Antimicrobial Activity

Preparation and in‐vitro Evaluation of 4‐Benzylsulfanylpyridine‐2‐carbohydrazides as Potential Antituberculosis Agents

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