SYNTHESIS AND ANTIMICROBIAL ACTIVITY OF NEW 1-R-3-(2-PIRIDYL)- 4-NITROSO- 5-CARBOXIETHYL-1H-PYRAZOLES. Stefania Aielloa , Carmelo Massimo Maidab, Fabio Venturellab, Diego Planetac Marco Giammancod, M.Milicib a Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo bDipartimento di Scienze per la Promozione della Salute G. D’ Alessandro, Università degli Studi di Palermo cDipartimento dei Sistemi Agro-Abientali,Università degli Studi di Palermo d Dipartimednto di Studi Giuridici, Economici, Biomedici e Psicosociopedagogici delle Scienze Motorie e Sportive, Università degli Studi di Palermo Corresponding author: Stefania Aiello, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari, Università degli Studi di Palermo, Via Archirafi 32, 90123 Palermo, Italy; tel:+39.091 23896802; email: email@example.com In recent years, epidemiological studies confirm the significant impact on human health by infections caused by pathogenic fungi. In fact, although the Candida genus is commensal and a constituent of the normal gut flora, it is responsible for opportunistic infections and can become pathogenic secondary to predisposing factors related to the host, like a comprimised immune system (AIDS, anti-cancer therapy, transplants), excessive prophylaxis with antimicrobial agents, and use of invasive catheters. Large-scale surveillance for fungal infections has demonstrated an increasing incidence of drug-resistant fungal pathogens. As a matter of fact, a significant number of fungi species (especially Candida glabrata and Candida krusei) exhibited primary resistance to Fluconazole or were less susceptible to Amphotericin B. Furthermore, as a consequence of the toxicity of the currently used polyene antifungal drugs, which leads to interrupt the therapy, and the emergence of Candida species resistance to azole-based agents, there is an urgent need for developing alternative drug therapies. In our previous study we have disclosed the synthesis and antifungal activity of a series of 4-nitrosopyrazoles that mainly displayed in vitro potent antifungal activity at no cytotoxic concentrations and that some of these compounds were 4 times more potent than Amphotericine B and Fluconazole respectively against Cryptococcus neoformans and Candida Krusei [1-4] As part of our Structure Activity Relationships studies, we were interested in learning the influence of the steric and electronic effects of the substituent in position 5 of the 4-nitrosopyrazoles which had already showed powerful antimycotic activity. Therefore, we synthetized title compounds and evaluated their antimycotic activity (fig1). NNNCOOC2H5ONR R: a=H, b= CH3, c=C2H5 Fig 1. Synthetized compounds The 5-carboxiethylester group has made the antimycotic actity dramatically decay, confirming the necessity, for a good antimicotic activity, of derivatives in which the position 5 is free or substituted with little groups as a methyl shown the best antifungal activity.  E. Aiello, S. Aiello, F. Mingoia, A. Bacchi, G. Pelizzi, C. Musiu, M. G. Setzu, A. Pani, P. La Colla and M. E. Marongiu. Synthesis and Antimicrobial activity of New 3-(1-R -3-methyl-4-nitroso-1H-5-pyrazolyl)-5-methylisoxazole derivatives, Bioorganic and Medicinal Chemistry, 2000, 8, 2719-2728  Stefania Aiello; Enrico Aiello, Marica Orioli, Marina Carini, 3-(1-R-3-methyl-4-nitroso-1H-5-pyrazolyl)-5-methylisoxazoles: a new class of antifungal compounds. In vitro metabolism by rat liver:LC and LC-MS studies. Convegno Nazionale, Sorrento 18-22 Settembre 2002.  S. Aiello, E. Aiello and M. Milici: “Synthesis and Antifungal Activity of new 3(5)-methyl-5(3)-(2-thiophenyl) and -(2-quinolyl)-1H-1-R-4-nitrosopyrazoles.Part V”. Polish-Austrian-German-Hungarian-Italian Joint Meeting on Medicinal Chemistry, Krakow, October 15-18, 2003  Stefania Aiello, Antonio Macchiarulo, Maria Milici and Enrico Aiello, Sintesi e studi QSAR di nuovi derivati 3(5)-(2-X)-1R-1H-4-nitrosopirazoli: una classe di composti con potente attività antifungina in vitro. Parte VI XVII Convegno Nazionale della Divisione di Chimica Farmaceutica della SCI, Pisa 6-10 settembre 2004.
|Titolo:||Synthesis and antimicrobial activity of new 1-R-3-(2-Piridyl)-4-nitroso-5 carboxiethyl-1H-Pyrazoles|
|Citazione:||Aiello, S., Maida, C., Venturella, F., Planeta, D., Giammanco, M., & Milici, M.Synthesis and antimicrobial activity of new 1-R-3-(2-Piridyl)-4-nitroso-5 carboxiethyl-1H-Pyrazoles.|
|Appare nelle tipologie:||6.2 Abstract non pubblicato|