Hay R J
St. John's Institute of Dermatology, Guy's Hospital, London, England.
J Am Acad Dermatol. 1994 Sep;31(3 Pt 2):S82-6. doi: 10.1016/s0190-9622(08)81275-3.
In the past 10 years there has been a major expansion in the development of antifungal drugs, but there are still weaknesses in the range and scope of current antifungal chemotherapy. New developments have included the modification of existing drug molecules to eliminate toxicity and improve activity, for instance, the development of the lipid formulations of the polyene antifungal agent amphotericin B. Three different amphotericin B derivatives, a unilamellar liposome (AmBisome), a colloidal dispersion (ABCD--Amphocil), and a lipid complex (ABLC) are undergoing evaluation. New triazoles with broad-spectrum antifungal activity, such as saperconazole, are also being assessed. The development of groups of drugs with novel modes of action such as cell wall biosynthesis inhibitors has been slower, although a number of molecules with activity against key enzymes, including chitin or glucan synthase, have been found. The morpholine antifungal amorolfine, a sterol biosynthesis inhibitor, has been developed for the topical treatment of fungal nail infections. The assessment of these drugs is a major challenge because it will be necessary to show that they have some advantage over existing compounds in efficacy, speed of action, or lack of toxicity.
在过去10年里，抗真菌药物的研发有了重大进展，但目前抗真菌化疗的种类和范围仍存在不足。新的进展包括对现有药物分子进行修饰以消除毒性并提高活性，例如，开发了多烯抗真菌剂两性霉素B的脂质制剂。三种不同的两性霉素B衍生物，即单层脂质体（安必素）、胶体分散体（两性霉素B胶体分散体——安福隆）和脂质复合物（两性霉素B脂质复合物）正在进行评估。具有广谱抗真菌活性的新型三唑类药物，如沙康唑，也在进行评估。尽管已经发现了一些对包括几丁质或葡聚糖合酶在内的关键酶有活性的分子，但作用方式新颖的药物组（如细胞壁生物合成抑制剂）的研发进展较慢。吗啉类抗真菌药阿莫罗芬是一种甾醇生物合成抑制剂，已被开发用于局部治疗甲癣。对这些药物进行评估是一项重大挑战，因为有必要证明它们在疗效、作用速度或无毒性方面比现有化合物具有某些优势。
