Anti-Candida, Anti-Enzyme Activity and Cytotoxicity of 3,5-Diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides

Abstract

Because of the need for more effective and less harmful antifungal therapies, and interest in the synthesis of new carboximidamides, the goal of this study was to determine the antifungal and anti-enzyme activities of some new pyrazole carboximidamides and their cytotoxicity. For this purpose, tests were performed to evaluate: minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC); production of proteinases and phospholipase, and cytotoxicity of the extracts. Data were analyzed by ANOVA and Tukey Tests (α = 5%). The results were: MIC and MFC ≥ 62.5 μg/mL (C. albicans, C. parapsilosis, C. famata, C. glabrata, and Rhodotorula mucillaginosa) and OPEN ACCESSMolecules 2014, 19 5807 MIC and MFC ≥ 15.6 μg/mL (C. lipolytica). The values of proteinase and phospholipase (Pz) of C. albicans before and after exposure to the compounds were: 0.6 (±0.024) and 0.2 (±0.022) and 0.9 (±0.074) and 0.3 (±0.04), respectively. These proteinase results were not significant (p = 0.69), but those of phospholipase were (p = 0.01), and 15.6 μg/mL was the most effective concentration. The cytotoxicity means were similar among the tests (p = 0.32). These compounds could be useful as templates for further development through modification or derivatization to design more potent antifungal agents. Data from this study provide evidence that these new pyrazole formulations could be an alternative source for the treatment of fungal infections caused by Candida. However, a specific study on the safety and efficacy of these in vivo and clinical trials is still needed, in order to evaluate the practical relevance of the in vitro results.

Retentive efficacy, antimicrobial and cytotoxicity comparisons between different types of commercial and experimental denture adhesives with antifungal action

“…The use of pyrazole has already been discussed in another study and its antimicrobial activity had been proven against different species of C. albicans. Low cytotoxicity has been detected 31) . Among antifungal agents, polyenes (Nystatin and Amphotericin B) and azoles (itraconazole, miconazole and clotrimazole) 44,45) are the therapeutic agents employed most for the topical treatment of oral candidiasis.…”

“…The synthesis and initial tests of antifungal activity are described by Oliveira et al 31) , wherefrom the initial antifungal concentration of pyrazole to be tested has been established.…”

“…These alternatives must be more effective, less toxic and cheaper 30) . One alternative comprises the new pyrazolinic compounds with activities against the microorganisms, low cytotoxicity and high yield, allowing their production on a large scale 31) . Heterocyclic compounds containing pyrazole have a broad spectrum of biological activities, such as monoamine oxidase inhibitor, anticonvulsant, antibacterial, hypotensive, antipyretic and anti-inflammatory activities 31) .…”

“…Several research groups have synthesized and evaluated pyrazoles against different biological agents 32) . Since 3,5-diaryl-4,5-dihydro-1H-pyrazole-1-carboximidamides have shown antimicrobial capacity and low cytotoxicity, they are an alternative source for the treatment of fungal infections caused by Candida 31,33) .…”

1,3,5-triaril-4,5-dihidro-1h-pirazol türevi bazı bileşiklerin benzodiazepin reseptörleri aracılıklı anksiyolitik-benzeri etkileri

“…4,5-dihidro-1H-pirazol türevilerinin terapötik etki potansiyellerini değerlendirmek üzere yapılan literatür taramalarında, bu bileşiklerin özellikle kemoterapötik [1][2][3][4] , antinosiseptif [5][6][7][8][9][10] , antiinflamatuar 5,9,[11][12][13] ve antipiretik 9,14 etkinlik yönünden kayda değer bir aktivite profilleri olduğu dikkati çekmektedir.…”