Integration of multiscale molecular modeling approaches with the design and discovery of fusidic acid derivatives.

Fusidic acid (FA) is an effective antibiotic against , but it is metabolically unstable.  14 derivatives were designed and synthesized by blocking the metabolic sites of FA (21-COOH and 3-OH) to maintain antibacterial activity and prolong the half-life. Six derivatives showed good antibacterial activity, and the pharmacokinetic experiments confirmed that two derivatives modified in 21-COOH released FA and showed longer half-lives than FA.