ABSTRACT
Twenty analogues of pentamidine, 7 primary metabolites of pentamidine, and 30 dicationic substituted bis-benzimidazoles were screened for their inhibitory and fungicidal activities against
Candida albicans
and
Cryptococcus neoformans
. A majority of the compounds had MICs at which 80% of the strains were inhibited (MIC
80
s) comparable to those of amphotericin B and fluconazole. Unlike fluconazole, many of these compounds were found to have potent fungicidal activity. The most potent compound against
C. albicans
had an MIC
80
of ≤0.09 μg/ml, and the most potent compound against
C. neoformans
had an MIC
80
of 0.19 μg/ml. Selected compounds were also found to be active against
Aspergillus fumigatus
,
Fusarium solani
,
Candida
species other than
C. albicans
, and fluconazole-resistant strains of
C. albicans
and
C. neoformans
. It is clear from the data presented here that further studies on the structure-activity relationships, mechanisms of action and toxicities, and in vivo efficacies of these compounds are warranted to determine their clinical potential.
摘要:对于20种戊二胺类似物、7种戊二胺的主要代谢产物以及30种二阳离子取代的双苯并咪唑类化合物进行了筛选,评估它们对念珠菌和隐球菌的抑制和杀真菌活性。大多数化合物的MIC(80%菌株被抑制的最小抑菌浓度)与两性霉素B和氟康唑相当。与氟康唑不同,许多这些化合物表现出强效的杀真菌活性。对于念珠菌而言,最有效的化合物的MIC80为≤0.09μg/ml,对于隐球菌而言,最有效的化合物的MIC80为0.19μg/ml。选择的化合物也对曲霉、索兰镰孢霉、除念珠菌外的其他种类的念珠菌,以及氟康唑耐药菌株的活性。从这里呈现的数据清楚地表明,有必要进行进一步的研究,以确定这些化合物的结构活性关系、作用机制和毒性,以及它们在体内的疗效,以确定它们的临床潜力。