Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents

Candida albicans represents the most prevalent microbial population in mucosal and systemic infections, usually confined to severely immunocompromised people. Considering the increase of resistant strains and the demand for new antifungal drugs endowed with innovative mechanism of action, we performed a ligand-based virtual screening in order to identify new anti-Candida compounds. Starting from a large library of natural/semisynthetic products and several published synthesized compounds, three coumarin derivatives were discovered in silico as new hit compounds and submitted to the in vitro assay in order to confirm their predicted biological activity.

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“…Actually, in literature, several works demonstrate the anti-fungal activity of coumarin derivatives [24][25][26][27][28][29] .…”

Section: Resultsmentioning

confidence: 99%

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Gidaro

Alcaro

Secci

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…significantly increased the antimicrobial efficacy and broadened the antimicrobial spectrum of activity of these compounds. 8 Although triazole drugs are extensively used as antifungal agents in clinics, 25 the combination of the triazole moiety with other pharmacophores is being investigated in order to develop new types of antifungal drugs, which might exert new mechanisms of action and be effective against multidrugresistant fungi. 26 In the current work, the importance of the peptide in maintaining the antifungal activity of the conjugate 4 has been demonstrated.…”

Section: Acs Medicinal Chemistry Lettersmentioning

confidence: 99%

“…7 Therefore, numerous efforts have focused on the development of coumarins as potential drugs. 8 The copper(I)-catalyzed azide−alkyne cycloaddition (CuAAC) reaction has previously been employed as a means of orthogonal modification of peptides. 9,10 CuAAC results in the formation of 1,4-disubstituted 1,2,3-triazoles, which are bioisosteres of the amide bond.…”

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confidence: 99%

Synthesis of a New Peptide–Coumarin Conjugate: A Potential Agent against Cryptococcosis

Ferreira

Carneiro

Lara

et al. 2015

ACS Med. Chem. Lett.

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Antimicrobial peptides (AMPs) are currently being investigated as potential sources of novel therapeutics against an increasing number of microorganisms resistant to conventional antibiotics. The conjugation of an AMP to other bioactive compounds is an interesting approach for the development of new derivatives with increased antimicrobial efficiency and broader spectra of action. In this work, the synthesis of a new peptide−coumarin conjugate via copper(I)-catalyzed azide−alkyne cycloaddition is described. The conjugate was assayed for in vitro cytotoxicity and displayed antifungal activity against Cryptococcus gattii and Cryptococcus neoformans. Additionally, the conjugate exhibited increased antifungal efficacy when compared with the individual peptide, coumarin, or triazole moieties. Treatment of C. gattii with the peptide−coumarin conjugate enhanced the production of reactive oxygen species, suggesting that the oxidative burst plays an important role in the mechanism of action of the conjugate. KEYWORDS: Antimicrobial peptide, copper(I)-catalyzed azide−alkyne cycloaddition, coumarin, cryptococcosis, reactive oxygen species A ntimicrobial peptides (AMPs) are small molecular weight proteins with antimicrobial activity against bacteria, viruses, and fungi. 1 AMPs are currently being investigated as potential sources of novel therapeutic antimicrobial agents because of their broad-spectrum activity and low susceptibility for developing resistance. 2 Ubiquicidin (UBI) is an antimicrobial peptide, which was first isolated from murine macrophages and then found at low concentrations (as a first line of defense) inside human airway epithelial cells, activated macrophages, and in human colon mucosa. UBI is a cationic peptide consisting of 59 amino acid residues. It is not expected to be immunogenic to humans since it is of human origin. 3 UBI 1−59 and some of its fragments have been shown to be microbicidal against a broad spectrum of pathogens. Of particular interest is the fragment UBI 31−38 (Figure 1), which is relatively small, easily synthesized, and exhibits antibacterial activity toward methicillin resistant Staphylococcus aureus. 4 Peptides open up new perspectives in drug design by providing an entire range of highly selective and nontoxic pharmaceuticals. With growing applications of their synthesis and bioactivity, considerable attention has been focused on the research of peptide-based derivatives. 5 Coumarins form an important class of benzopyrones, which are found in nature. Many coumarins and their derivatives possess antimicrobial, anti-inflammatory, and anticancer properties. 6 Research on coumarin compounds as antifungal agents has shown that structural modification of the coumarin skeleton (i.e., the benzene ring, lactone ring, or both) results in derivatives, which possess potent antifungal activity when compared to clinically used antifungal drugs. 7 Therefore, numerous efforts have focused on the development of coumarins as potential drugs. 8 The copper(I)-catalyzed azide−alkyne cyclo...

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“…Coumarins form an important class of compounds, which occupy a special role in nature 13,14 . The presence of coumarin architecture in naturally occurring phytoconstituents with anticancer 15,16 , anti-HIV 17 , antituberculosis 18 , anti-influenza 19 , antialzheimer 20,21 , anti-inflammatory 22 , antiviral 23 , antimicrobial 13 and xanthine oxidase inhibitory activities [24][25][26] makes it a privileged structure.…”

Section: Introductionmentioning

confidence: 99%

“…The presence of coumarin architecture in naturally occurring phytoconstituents with anticancer 15,16 , anti-HIV 17 , antituberculosis 18 , anti-influenza 19 , antialzheimer 20,21 , anti-inflammatory 22 , antiviral 23 , antimicrobial 13 and xanthine oxidase inhibitory activities [24][25][26] makes it a privileged structure. Among the diverse array of biological activities possessed by coumarins, we are particularly interested towards their xanthine oxidase inhibitory potential which has also been extensively explored [24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and evaluation of 2,4-diarylpyrano[3,2-c]chromen-5(4H)-one as a new class of non-purine xanthine oxidase inhibitors

Virdi

Sharma

Mehndiratta

et al. 2015

Journal of Enzyme Inhibition and Medicinal Chemistry

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Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents

Cited by 239 publications

References 18 publications

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Identification of new anti-Candida compounds by ligand-based pharmacophore virtual screening

Synthesis of a New Peptide–Coumarin Conjugate: A Potential Agent against Cryptococcosis

Design, synthesis and evaluation of 2,4-diarylpyrano[3,2-c]chromen-5(4H)-one as a new class of non-purine xanthine oxidase inhibitors

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