Novel small molecules for the treatment of infections caused by Candida albicans: a patent review (2002-2010)

被引:26
作者
Calugi, Chiara [1 ]
Trabocchi, Andrea [1 ]
Guarna, Antonio [1 ]
机构
[1] Univ Florence, Dept Chem Ugo Schiff, I-50019 Florence, Italy
关键词
aspartyl proteases; azoles; drug resistance; echinocandin; fungal infections; glucan synthase; peptidomimetics; polyenes; SECRETED ASPARTYL PROTEINASES; ELONGATION-FACTOR; 2; AMPHOTERICIN-B; ANTIFUNGAL ACTIVITY; NIKKOMYCIN-Z; SUBINHIBITORY CONCENTRATIONS; ANTIMICROBIAL PEPTIDES; INVASIVE CANDIDIASIS; VIRULENCE FACTOR; DRUG-RESISTANCE;
D O I
10.1517/13543776.2011.551116
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction: The fungal pathogen Candida albicans is one of the leading causes of infections affecting immunodeficient individuals, including those HIV-infected and patients undergoing cancer therapy. Emerging problems in terms of therapeutic efficacy and drug resistance have highlighted the need to consider new therapeutic approaches, based on the exploitation of virulence factors as alternatives to conventional drug targets. Areas covered: Advances in the development of anti-Candida drugs are examined in this review, as reflected by the patent literature since 2002 along with selected peer-reviewed publications. Taking into account a total of 26 patents, the discussion encompasses several therapeutic approaches, including azoles as ergosterol biosynthesis inhibitors, glucan and chitin synthase inhibitors, and secreted aspartyl protease inhibitors. Expert opinion: New analogs of existing drugs are being developed as broad spectrum antifungals to improve efficacy and circumvent drug resistance. Also, candidate drugs targeting new virulence factors are promising to overcome limitations due to poor efficacy and the rising of drug resistance observed for several available drugs. Efforts for the discovery and development of antifungal agents should be equivalent to other therapeutic areas, and advances in the generation of therapeutic agents with fungus-specific mechanisms of action are of highest priority.
引用
收藏
页码:381 / 397
页数:17
相关论文
共 102 条
[1]  
AbadZapatero C, 1996, PROTEIN SCI, V5, P640
[2]   An update on antifungal targets and mechanisms of resistance in Candida albicans [J].
Akins, RA .
MEDICAL MYCOLOGY, 2005, 43 (04) :285-318
[3]  
Alekshun MN., 2004, DRUG DISCOV TODAY TH, V1, P483, DOI DOI 10.1016/J.DDSTR.2004.10.006
[4]   Bacterial virulence as a target for antimicrobial chemotherapy [J].
Alksne, LE ;
Projan, SJ .
CURRENT OPINION IN BIOTECHNOLOGY, 2000, 11 (06) :625-636
[5]   Biosynthesis of glycoproteins in Candida albicans:: Activity of mannosyl and glucosyl transferases [J].
Arroyo-Flores, BL ;
Rodríguez-Bonilla, J ;
Villagómez-Castro, JC ;
Calvo-Méndez, C ;
Flores-Carreón, A ;
López-Romero, E .
FUNGAL GENETICS AND BIOLOGY, 2000, 30 (02) :127-133
[6]  
ASTELLAS PHARM INC, 2010, Patent No. 2204379
[7]  
ASTELLAS PHARM INC, 2009, Patent No. 131246
[8]  
AVENTIS PHARM S A, 2003, Patent No. 006436
[9]  
BANYU SEIYAKU KK, 1994, Patent No. 6157582
[10]   Synthesis, biological evaluation, and pharmacophore generation of new pyridazinone derivatives with affinity toward α1- and α2-adrenoceptors [J].
Barbaro, R ;
Betti, L ;
Botta, M ;
Corelli, F ;
Giannaccini, G ;
Maccari, L ;
Manetti, F ;
Strappaghetti, G ;
Corsano, S .
JOURNAL OF MEDICINAL CHEMISTRY, 2001, 44 (13) :2118-2132