Setti E L, Micetich R G
Axys Pharmaceuticals, Inc., South San Francisco, California 94080, USA.
EXS. 2000;89:29-53. doi: 10.1007/978-3-0348-8393-1_3.
So far, two strategies have been applied to develop new anti-infective agents: (a) the synthesis of analogs of classical antibiotics with enhanced activity against resistant pathogens and (b) the screening of naturally occurring substances and libraries of synthetic compounds for antimicrobial activity in whole-cell assays. Today, the same principles are being used; however, the search for antimicrobial compounds with novel modes of action is based on targeting specific resistance and virulence factors. Novel targets for anti-infective agents are currently being discovered as a consequence of a better understanding of cell biology, the molecular basis of bacterial resistance, the gene-pathogenicity relationship and the mechanism of the infection process.
到目前为止,已应用两种策略来开发新型抗感染药物:(a) 合成对耐药病原体具有增强活性的经典抗生素类似物,以及 (b) 在全细胞试验中筛选天然存在的物质和合成化合物文库的抗菌活性。如今,仍在使用相同的原则;然而,寻找具有新型作用模式的抗菌化合物是基于针对特定的耐药性和毒力因子。由于对细胞生物学、细菌耐药性的分子基础、基因-致病性关系以及感染过程机制有了更好的理解,目前正在发现抗感染药物的新靶点。