Novel 4-Methoxynaphthalene-
            <i>N</i>
            -Acylhydrazones As Potential for Paracoccidioidomycosis and Tuberculosis Co-Infection

Rozada, Andrew M.F.; Rodrigues, Franciele A V; Sampiron, Eloísa G; Seixas, Flávio Augusto Vicente; Basso, Ernani A.; Scodro, Regiane Bertin de Lima; Kioshima, Érika Seki; Gauze, Gisele F.

doi:10.2217/fmb-2018-0357

Cited by 20 publications

(15 citation statements)

References 32 publications

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“…N -Acylhydrazone (NAH) scaffold has been identified as a lead pharmacophore in many bioactive compounds that act against different molecular targets [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. This moiety is a putative bioisostere of amide backbone [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

et al. 2021

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In this article, a synthesis of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides and their structural interpretation by NMR experiments is described in an attempt to explain the duplication of some peaks in their 1H- and 13C-NMR spectra. Twenty new 6-methyl-1H-pyrazolo[3,4-b]quinoline substituted N-acylhydrazones 6(a–t) were synthesized from 2-chloro-6-methylquinoline-3-carbaldehyde (1) in four steps. 2-Chloro-6-methylquinoline-3-carbaldehyde (1) afforded 6-methyl-1H-pyrazolo[3,4-b]quinoline (2), which upon N-alkylation yielded 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetate (3). The hydrazinolysis of 3 followed by the condensation of resulting 2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazide (4) with aromatic aldehydes gave N-acylhydrazones 6(a–t). Structures of the synthesized compounds were established by readily available techniques such as FT-IR, NMR and mass spectral studies. The stereochemical behavior of 6(a–t) was studied in dimethyl sulfoxide-d6 solvent by means of 1H NMR and 13C NMR techniques at room temperature. NMR spectra revealed the presence of N’-(benzylidene)-2-(6-methyl-1H-pyrazolo[3,4-b]quinolin-1-yl)acetohydrazides as a mixture of two conformers, i.e., E(C=N)(N-N) synperiplanar and E(C=N)(N-N)antiperiplanar at room temperature in DMSO-d6. The ratio of both conformers was also calculated and E(C=N) (N-N) syn-periplanar conformer was established to be in higher percentage in equilibrium with the E(C=N) (N-N)anti-periplanar form.

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Section: Introductionmentioning

confidence: 99%

“…1 Aryl protons excluding H-3 and H-4 of pyrazoloquinoline 2. Signal overlapped by aromatic signals 3.…”

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confidence: 99%

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

et al. 2021

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“…Molecular docking techniques have been used to accelerate the drug development process, focused on the essential proteins or those important for the pathogenicity of infectious agents [11,29,30]. In this context, the proteins involved in the establishment of C. albicans infection, such as virulence factors associated with capacity for adhesion and invasion of host tissues, are promising.…”

Section: Discussionmentioning

confidence: 99%

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

Sá

Silva

Neto

et al. 2020

Journal of Medical Microbiology

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This study evaluated the effect of etomidate against biofilms of Candida spp. and analysed through molecular docking the interaction of this drug with ALS3, an important protein for fungal adhesion. Three fluconazole-resistant fungi were used: Candida albicans, Candida parapsilosis and Candida tropicalis. Growing biofilms were exposed to etomidate at 31.25–500 µg ml−1. Then, an ALS3 adhesive protein from C. albicans was analysed through a molecular mapping technique, composed of a sequence of algorithms to perform molecular mapping simulation based on classic force field theory. Etomidate showed antifungal activity against growing biofilms of resistant C. albicans, C. parapsilosis and C. tropicalis at all concentrations used in the study. The etomidate coupling analysis revealed three interactions with the residues of interest compared to hepta-threonine, which remained at the ALS3 site. In addition, etomidate decreased the expression of mannoproteins on the surface of C. albicans. These results revealed that etomidate inhibited the growth of biofilms.

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“…The molecule HS9 (Zinc2123137) presented fungicidal activity that was more promising than HS2, with MIC values of 23.44 μM and low cytotoxicity in human cell lines [153]. Two recent studies indicate the synthesis of lead molecules from these hit molecules selected by virtual screening [154,155].…”

Section: Virtual Screeningmentioning

confidence: 99%

One Century of Study: What We Learned about Paracoccidioides and How This Pathogen Contributed to Advances in Antifungal Therapy

Kioshima

Mendonca

Teixeira

et al. 2021

JoF

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Paracoccidioidomycosis (PCM) is a notable fungal infection restricted to Latin America. Since the first description of the disease by Lutz up to the present day, Brazilian researchers have contributed to the understanding of the life cycle of this pathogen and provided the possibility of new targets for antifungal therapy based on the structural and functional genomics of Paracoccidioides. In this context, in silico approaches have selected molecules that act on specific targets, such as the thioredoxin system, with promising antifungal activity against Paracoccidioides. Some of these are already in advanced development stages. In addition, the application of nanostructured systems has addressed issues related to the high toxicity of conventional PCM therapy. Thus, the contribution of molecular biology and biotechnology to the advances achieved is unquestionable. However, it is still necessary to transcend the boundaries of synthetic chemistry, pharmaco-technics, and pharmacodynamics, aiming to turn promising molecules into newly available drugs for the treatment of fungal diseases.

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Novel 4-Methoxynaphthalene- N -Acylhydrazones As Potential for Paracoccidioidomycosis and Tuberculosis Co-Infection

Cited by 20 publications

References 32 publications

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

Synthesis of Novel N-Acylhydrazones and Their C-N/N-N Bond Conformational Characterization by NMR Spectroscopy

Antifungal activity of etomidate against growing biofilms of fluconazole-resistant Candida spp. strains, binding to mannoproteins and molecular docking with the ALS3 protein

One Century of Study: What We Learned about Paracoccidioides and How This Pathogen Contributed to Advances in Antifungal Therapy

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