Daneshtalab Mohsen
School of Pharmacy, Memorial University of Newfoundland, St. John's, Canada.
J Pharm Pharm Sci. 2008 Jul 6;11(2):44s-55s. doi: 10.18433/j3h010.
Life-threatening fungal infections have increased dramatically in recent decades in immunocompromised patients. An estimated 40% of all deaths from hospital-acquired infections are due to infections caused by opportunistic fungi. The current treatment options are either causing serious toxicity, or becoming inactive against the drug-resistant fungal strains. Thus, the discovery and development of new antifungal agents that are economically feasible, have excellent therapeutic value, and address the problems of toxicity and species resistance is very important. We have recently designed and synthesized a series of chlorogenic acid-based peptidimimetics using structure-based methodology starting with cyclic peptides of the candin class of antifungals. These novel and totally synthetic compounds exhibit promising antifungal activity against pathogenic fungi with very low toxicity against brine shrimps. The possible novelty in their mechanism of action and economically feasible synthetic approach are the attractive features of this class of compounds that make them different from the already utilized antifungal agents.
近几十年来，危及生命的真菌感染在免疫功能低下的患者中急剧增加。据估计，医院获得性感染导致的所有死亡中，约40%是由机会性真菌引起的感染所致。目前的治疗选择要么会导致严重的毒性，要么对耐药真菌菌株失去活性。因此，发现和开发经济可行、具有优异治疗价值且能解决毒性和物种耐药问题的新型抗真菌药物非常重要。我们最近使用基于结构的方法，从抗真菌药物坎地菌素类的环肽开始，设计并合成了一系列基于绿原酸的肽模拟物。这些新型的全合成化合物对致病真菌表现出有前景的抗真菌活性，而对卤虫的毒性非常低。其作用机制可能的新颖性以及经济可行的合成方法是这类化合物的吸引人之处，使其有别于已使用的抗真菌药物。
