Leishmanicidal Activity of New Megazol Derivatives

Riente, Roselene Ribeiro; Souza, Vanessa Pereira de; Carvalho, Samir A.; Kaiser, Marcel; Brun, Reto; Silva, E. F. da

doi:10.2174/157340609788681467

Cited by 5 publications

(3 citation statements)

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“…In stark contrast, compounds ( 3 : aryl = furan‐2‐yl, thien‐2‐yl, pyrrol‐2‐yl, or imidazol‐2‐yl) are all inactive. Specific nitro‐substituted five‐membered ring heteroaromatics, e.g., megazol, have been known for many years to possess useful biological activities, mainly against parasites and bacterias . The mechanism of action of these compounds is based on their ready reduction to radical intermediates using a flavine‐based enzyme, present in the intracellular media.…”

Section: Resultsmentioning

confidence: 99%

Anti‐Tuberculosis Evaluation and Conformational Study of N‐Acylhydrazones Containing the Thiophene Nucleus

Castro

Bispo

Kaiser

et al. 2014

Archiv der Pharmazie

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A series of N-acylhydrazonyl-thienyl derivatives (compounds 2 and 3), mainly of the type 2-(aryl-CH=N-NHCOCH2 )-thiene (2: aryl = substituted-phenyl; 3: aryl = heteroaryl) were evaluated against Mycobacterium tuberculosis. Particularly active compound was 3 (heteroaryl = 5-nitrothien-2-yl or 5-nitrofuran-2-yl) with MIC values of 8.5 and 9.0 μM, respectively. Moderately active compounds were compound 3 (heteroaryl = pyridin-2-yl) and compound 2 containing aryl = 2- or 4-hydroxyphenyl groups, with MIC values between 170 and 408 μM. Compound 2 containing OMe, H, F, Cl, Br, CN, and NO2 substituents and compound 3 (heteroaryl = furan-2-yl, thien-2-yl, pyrrol-2-yl, imidazol-2-yl, pyridin-3-yl, and pyridin-4-yl) were all inactive. Clearly, there is no correlation of activity with the electronic effects of the substituents. The activities suggest different modes of biological action of the compounds having nitro-heteroaryl groups, on the one hand, and the 2-hydroxyphenyl or pyridin-2-yl substituents, on the other hand. Compounds having 2- or 4-hydroxyphenyl, 2-hydroxy-5-nitrophenyl, or 4-hydroxy-3-chlorophenyl were less cytotoxic than ethambutol. It is important to notice that compound 3 (aryl = 5-NO2 -furan-2-yl) exhibited a promising therapeutic index (TI = 1093.90), with a value 4.4 less than that of ethambutol. Compounds 2 and 3 exist in DMSO or MeOD solutions as mixtures of EC(O)N /EC=N and ZC(O)N /EC=N conformers.

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Section: Resultsmentioning

confidence: 99%

Anti‐Tuberculosis Evaluation and Conformational Study of N‐Acylhydrazones Containing the Thiophene Nucleus

Castro

Bispo

Kaiser

et al. 2014

Archiv der Pharmazie

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show abstract

“…184 Additionally, the synthesis of hybrids of the nitro-containing antiprotozoal agent megazol and the antileishmanial combretastatin-type pharmacophore, yielded compound 55 that demonstrated potent activity against L. donovani axenic amastigotes with an EC 50 value of 0.08 μg/mL and an SI value of 240. 185 3.2.4.7. Phospholipids.…”

Section: Antileishmanials From Phenotypic Effortsmentioning

confidence: 99%

“…The synthesis of structural hybrids, utilizing the nitro-furan moiety as found in the antitrypanosomal agent nifurtimox and the antileishmanial benzamidine pharmacophore, yielded two highly potent derivatives ( 54 ) (Figure ) with activity against L. major promastigotes and intracellular amastigotes . Additionally, the synthesis of hybrids of the nitro-containing antiprotozoal agent megazol and the antileishmanial combretastatin-type pharmacophore, yielded compound 55 that demonstrated potent activity against L. donovani axenic amastigotes with an EC 50 value of 0.08 μg/mL and an SI value of 240 …”

Section: Drug Discovery For Leishmaniasismentioning

confidence: 99%