New Lead Structures in Antifungal Drug Discovery
Current Medicinal Chemistry, 2011, 18, 733-766
733
New Lead Structures in Antifungal Drug Discovery
Chunquan Sheng and Wannian Zhang*
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road,
Shanghai 200433, People’s Republic of China
Abstract: During the past two decades, the incidence of invasive fungal infections has been increasing dramatically.
Clinical available antifungal agents have several drawbacks such as limited potency and spectrum, drug related toxicity, non-optimal pharmacokinetics, and severe resistance. There is an emergent need to develop new antifungal drugs with novel chemical structures and novel mechanism of action. This review will focus on the most significant achievements in the discovery of antifungal lead structures within last few years. In particular, we pay more attention on the structureactivity relationship of antifungal leads and provide perspectives for future antifungal drug discovery.
Keywords: Antifungal, lead compounds, structure-activity relationship, rational drug design.
1. INTRODUCTION
Fungi represent a diverse group of eukaryotic organisms that are heterotrophic and devoid of chlorophyll. It is estimated that about 600 species of fungi are associated with human disease, with about 20 that cause more than 99% of human fungal infections. In general, fungal infections can be classified into two types: superficial fungal infection and invasive fungal infection. Superficial fungal infections often affect the skin or mucous membranes. They are very common with worldwide distribution and can be treated successfully by tropical antifungal drugs such as miconaozle, bifonazole and terbinafine [1]. On the other hand, invasive fungal infections are often life-threatening. During the past two decades, the incidence of invasive fungal infections and associated mortality has been increasing dramatically [2-4].
This situation can be attributed to the increase
733
New Lead Structures in Antifungal Drug Discovery
Chunquan Sheng and Wannian Zhang*
Department of Medicinal Chemistry, School of Pharmacy, Second Military Medical University, 325 Guohe Road,
Shanghai 200433, People’s Republic of China
Abstract: During the past two decades, the incidence of invasive fungal infections has been increasing dramatically.
Clinical available antifungal agents have several drawbacks such as limited potency and spectrum, drug related toxicity, non-optimal pharmacokinetics, and severe resistance. There is an emergent need to develop new antifungal drugs with novel chemical structures and novel mechanism of action. This review will focus on the most significant achievements in the discovery of antifungal lead structures within last few years. In particular, we pay more attention on the structureactivity relationship of antifungal leads and provide perspectives for future antifungal drug discovery.
Keywords: Antifungal, lead compounds, structure-activity relationship, rational drug design.
1. INTRODUCTION
Fungi represent a diverse group of eukaryotic organisms that are heterotrophic and devoid of chlorophyll. It is estimated that about 600 species of fungi are associated with human disease, with about 20 that cause more than 99% of human fungal infections. In general, fungal infections can be classified into two types: superficial fungal infection and invasive fungal infection. Superficial fungal infections often affect the skin or mucous membranes. They are very common with worldwide distribution and can be treated successfully by tropical antifungal drugs such as miconaozle, bifonazole and terbinafine [1]. On the other hand, invasive fungal infections are often life-threatening. During the past two decades, the incidence of invasive fungal infections and associated mortality has been increasing dramatically [2-4].
This situation can be attributed to the increase