Synthesis and biological evaluation of N-alkyl naphthoimidazoles derived from β-lapachone against Trypanosoma cruzi bloodstream trypomastigotes

Silva, Ari Miranda da; Araújo-Silva, Leonardo; Bombaça, Ana Cristina S.; Menna-Barreto, Rubem Figueiredo Sadok; Rodrigues-Santos, Cláudio Eduardo; Ferreira, Aurélio B. B.; Castro, Solange L. de

doi:10.1039/c7md00069c

Cited by 10 publications

(8 citation statements)

References 49 publications

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“…These results suggest an optimal lipophilicity range to the trypanocidal activity that may be related to the ability of these molecules to cross cell membranes. Similar correlations with different series of compounds have been observed by other authors such as Silva et al 51 These authors studied the tripanocidal activity of 1-N-and 3-N-alkyl-naphthoimidazoles.…”

Section: Biological Assayssupporting

confidence: 86%

Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles

Franklim¹,

Freire-de-Lima²,

Chaves³

et al. 2019

J. Braz. Chem. Soc.

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Chagas disease is a neglected tropical disease caused by the hemoflagellated parasite Trypanosoma cruzi (Kinetoplastida). The only available drug to treat chagasic patients in Brazil, the nitroheterocycle benznidazole, is effective solely during the acute phase of the infection. There is accordingly a need to develop new therapeutic tools for the treatment of Chagas disease. This work reports the synthesis, trypanocidal evaluation and human serum albumin (HSA) interactions of a novel series of 1,2,4-triazoles. The new derivatives were synthesized via microwave irradiation in good yields. Most compounds showed toxic effects against T. cruzi with low toxicity to host cells. Three S-alkylated-triazoles showed the best activity profile against amastigotes, with half maximal inhibitory concentration (IC 50) values of 3.95 ± 1.41, 4.15 ± 0.92 and 3.61 ± 0.65 μmol L-1 , respectively. The interaction between HSA and 3-[(1E,3E)-4-(1,3-benzodioxol-5-yl)buta-1,3-dien-1-yl]-5-(butylthio)-4-cyclohexyl-4,5-dihydro-1H-1,2,4-triazole was investigated using multiple spectroscopic techniques and molecular docking, revealing that serum albumin is a potential endogenous carrier to this compound in the human bloodstream.

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Section: Biological Assayssupporting

confidence: 86%

Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles

Franklim¹,

Freire-de-Lima²,

Chaves³

et al. 2019

J. Braz. Chem. Soc.

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“…Lapimidazoles were responsible for increasing oxidative stress by up to 4-fold in treated parasites, and they were the leading cause of ultrastructural phenotypes as previously reported. [75] The antioxidant urate partially re-established the mitochondrial metabolism only in 36-treated parasites, although lapimidazoles enormously reduced the O 2 uptake and mitochondrial complex activity. MitoTEMPO, a mitochondrialtargeted antioxidant, protected the efficiency of mitochondria in 136-and 167-treated parasites.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 98%

“…Although the synthetic methodology used to obtain imidazoles and oxazoles from β-lapachone (15) is well established, in 2017 Castro and co-workers reported a valuable modification to the traditional approach (Scheme 21). [75] The reaction was performed using ammonium acetate supported on basic alumina (SAA-BA), using a simple domestic microwave oven, where the desired products were successfully obtained in less than 15 min of reaction. This new methodology was also applied to obtain the lapimidazoles 170-174.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

“…Pinto's group published QSAR studies applied to compounds 171, 172, and 174 as well as 29 aryllapimidazoles with electron-donating or electron-withdrawing groups at positions 2, 3, and 4. [38,74] Based on these studies, Castro and co-workers [75] did not observe an obvious correlation between the substituent and the trypanocidal activity. However, a correlation with σ i (inductive effect substituent constant) was observed, from which it was perceived that the most active compounds presented very small or negative σ i values.…”

Section: P E R S O N a L A C C O U N T T H E C H E M I C A L R E C O R Dmentioning

confidence: 99%

“…Although the synthetic methodology used to obtain imidazoles and oxazoles from β‐lapachone ( 15 ) is well established, in 2017 Castro and co‐workers reported a valuable modification to the traditional approach (Scheme 21). [75] …”

Section: Biological Activitymentioning

confidence: 99%

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Imidazoles and Oxazoles from Lapachones and Phenanthrene‐9,10‐dione: A Journey through their Synthesis, Biological Studies, and Optical Applications

Dias

Paz

Nunes

et al. 2021

The Chemical Record

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Diverse structural frameworks are found in natural compounds and are well known for their chemical and biological properties; such compounds include the imidazoles and oxazoles. Researchers worldwide are continually working on the development of methods for synthesizing new molecules bearing these basic moiety and evaluating their properties and applications. To expand the knowledge related to azoles, this review summarizes important examples of imidazole and oxazole derivatives from 1,2-dicarbonyl compounds, such as lapachones and phenanthrene-9,10-diones, not only regarding their synthesis and biological applications but also their photophysical properties and uses. The data concerning the latter are particularly scarce in the literature, which leads to underestimation of the potential applications that can be envisaged for these compounds.

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Cu‐Catalyzed Chan–Evans–Lam Coupling Reactions of 2‐Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S. pneumoniae

Raju

Sheridan

Hauer

et al. 2022

Chemistry & Biodiversity

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The coupling of phenylboronic acids with poorly-activated imidazoles is studied as a model system to explore the use of copper-catalyzed Chan -Evans-Lam (CEL) coupling for targeted CÀ N bond forming reactions. Optimized CEL reaction conditions are reported for four phenanthroline-based ligand systems, where the ligand 4,5-diazafluoren-9-one (dafo, L2) with 1 molar equivalent of potassium carbonate yielded the highest reactivity. The substrate 2-nitroimidazole (also known as azomycin) has documented antimicrobial activity against a range of microbes. Here N-arylation of 2-nitroimidazole with a range of aryl boronic acids has been successfully developed by copper(II)-catalyzed CEL reactions. Azomycin and a range of newly arylated azomycin derivatives were screened against S. pneumoniae, where 1-(4-(benzyloxy)phenyl)-2-nitro-1H-imidazole (3d) was demonstrated to have a minimal inhibition concentration value of 3.3 μg/mL.

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Synthesis and biological evaluation of N-alkyl naphthoimidazoles derived from β-lapachone against Trypanosoma cruzi bloodstream trypomastigotes

Cited by 10 publications

References 49 publications

Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles

Design, Synthesis, Trypanocidal Activity, and Studies on Human Albumin Interaction of Novel S-Alkyl-1,2,4-triazoles

Imidazoles and Oxazoles from Lapachones and Phenanthrene‐9,10‐dione: A Journey through their Synthesis, Biological Studies, and Optical Applications

Cu‐Catalyzed Chan–Evans–Lam Coupling Reactions of 2‐Nitroimidazole with Aryl Boronic Acids: An Effort toward New Bioactive Agents against S. pneumoniae

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