Synthesis, activity, and docking studies of eugenol‐based glucosides as new agents against <i>Candida</i> sp.

Hipólito, Taciane Maíra Magalhães; Bastos, Guilherme Tadeu Lemos; Barbosa, Thúlio Wliandon Lemos; Souza, Thiago Belarmino de; Coelho, Luiz Felipe Leomil; Dias, Amanda Latércia Tranches; Rodríguez, Ihosvany Camps; Santos, Marcelo H. dos; Dias, Danielle Ferreira; Franco, Letícia Paiva; Carvalho, Diogo Teixeira

doi:10.1111/cbdd.13318

Cited by 30 publications

(21 citation statements)

References 34 publications

(36 reference statements)

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“…Therefore, modification of its chemical structure is sought out to be an important strategy to obtain molecules with desirable physicochemical and improved biological properties 5,9,10 . The enhanced antimicrobial activity of eugenol by its derivatisation has already been reported [11][12][13] . Recently, new Mannich base-type derivatives of eugenol were found to possess antifungal activity even equivalent to fluconazole 14 .…”

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confidence: 84%

Cellular apoptosis and necrosis as therapeutic targets for novel Eugenol Tosylate Congeners against Candida albicans

Lone

Wani

Fru

et al. 2020

Sci Rep

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Despite the rise of new Candida species, Candida albicans tops the list with high morbidity and mortality rates. to tackle this problem there is a need to explore new antifungals that could replace or augment the current treatment options. We previously reported that tosylation of eugenol on hydroxyl group resulted in molecules with enhanced antifungal potency. in line with that work, we synthesized new eugenol tosylate congeners (ETC-1-ETC-7) with different substituents on pendent sulfonyl group and tested their susceptibility against different fluconazole susceptible and resistant C. albicans strains. We evaluated physiology and mode of cell death in response to the most active derivatives by analyzing major apoptotic markers in yeast such as phosphatidylserine externalization, DnA fragmentation, mitochondrial depolarization and decrease in cytochrome c oxidase activity. the results demonstrated that all C. albicans strains were variably susceptible to the test compounds with Mic ranging from 0.125-512 µg/ml, and the most active compounds (ETC-5, ETC-6 and ETC-7) actuate apoptosis and necrosis in Candida cells in a dose-dependent manner via metacaspase-dependent pathway. Furthermore haemolytic assay showed low cytotoxicity effect of these ETCs. Overall the results indicated that etcs exhibit potential antifungal activity against C. albicans by activating apoptotic and necrotic pathways.

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confidence: 84%

Cellular apoptosis and necrosis as therapeutic targets for novel Eugenol Tosylate Congeners against Candida albicans

Lone

Wani

Fru

et al. 2020

Sci Rep

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“…Pharmacological properties of eugenol have been extensively highlighted, especially involving its antibacterial and antifungal properties [17–22] . Our research group has previously demonstrated that synthetic compounds obtained from natural phenylpropanoids, such as eugenol or its analogs (dihydroeugenol and isoeugenol), have important antimicrobial activity and that hybrids obtained from phenylpropanoids and sulfonamide moieties have important antitumor activity [23–30] . Taking advantage of the molecular hybridization strategy (and the well‐established antibacterial potential of eugenol and sulfonamide‐based drugs separately) herein we present for the first time the antibacterial activity of eugenol and dihydroeugenol‐based hybrids bearing the sulfonamide functionality ( Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Design, Synthesis, Antimicrobial Evaluation and in Silico Studies of Eugenol‐Sulfonamide Hybrids

Azevedo-Barbosa

Vale

Rossi

et al. 2021

Chemistry & Biodiversity

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Using molecular hybridization, specific sulfonamide derivatives of eugenol were synthesized with subtle modifications in the allylic chain of the eugenol subunit (and also in the nature of the substituent group in the sulfonamide aromatic ring) which allowed us to study the influence of structural changes on the antimicrobial potential of the hybrids. Antimicrobial test results showed that most of the synthesized hybrid compounds showed good activity with better results than the parent compounds. Molecular docking studies of the hybrids with the essential bacterial enzyme DHPS showed complexes with low binding energies, suggesting that DHPS could be a possible target for the antibacterial sulfonamide‐eugenol hybrids. Furthermore, most of the final compounds presented similar docking poses to that of the crystallographic ligand sulfamethoxazole. The results obtained allow us to conclude that these are promising compounds for use as new leads in the search for new antibacterial sulfonamides.

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“…In the late 1960s, there was a dramatic increase in fungal infections because of the development of antibiotic therapies (Vandeputte, Ferrari, & Coste, 2012), which represents a serious problem today. However, the number of antimicrobial medicines is limited, and it does not satisfy | 1187 JOAQUIM et Al. the need due to limitations related to the spectrum of action, potency, pharmacokinetic properties, and the emergent resistance of fungi and bacteria (Hipólito et al, 2018;Nett & Andes, 2016;Patil et al, 2018;Tobudic, Kratzer, & Presterl, 2012). In this context, the search and development of new antimicrobial therapies is imperative.…”

Section: Introductionmentioning

confidence: 99%

Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines

et al. 2018

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The combination of tools such as time‐kill assay with subsequent application of mathematical modeling can clarify the potential of new antimicrobial compounds, since minimal inhibitory concentration (MIC) value does not provide a very detailed characterization of antimicrobial activity. Recently, our group has reported that the 8‐hydroxy‐5‐quinolinesulfonic acid presents relevant antifungal activity. However, its intrinsic acidity could lead to an ionization process, decreasing fungal cell permeability. To overcome this potential problem and enhance activity, the purpose of this study was to synthesize and evaluate a novel series of hybrids between the 8‐hydroxyquinoline core and sulfonamide and to prove their potential using broth microdilution method, obtaining the pharmacodynamic parameters of the most active derivatives combining time‐kill studies and mathematical modeling and evaluating their toxicity. Compound 5a was the most potent, being active against all the fungal species tested, with low toxicity in normal cells. 5a and 5b have presented important antibacterial activity against Staphylococcus aureus strain. The EC50 values obtained by combination of time‐kill studies with mathematical model were similar to those of MIC, which confirms the potential of compounds. In addition, these derivatives are non‐irritant molecules with the absence of topical toxicity. Finally, 5a and 5b are promising candidates for treatment of dermatomycosis and candidiasis.

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Synthesis, activity, and docking studies of eugenol‐based glucosides as new agents against Candida sp.

Cited by 30 publications

References 34 publications

Cellular apoptosis and necrosis as therapeutic targets for novel Eugenol Tosylate Congeners against Candida albicans

Cellular apoptosis and necrosis as therapeutic targets for novel Eugenol Tosylate Congeners against Candida albicans

Design, Synthesis, Antimicrobial Evaluation and in Silico Studies of Eugenol‐Sulfonamide Hybrids

Rapid tools to gain insights into the interaction dynamics of new 8‐hydroxyquinolines with few fungal lines

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