Chemical modification of capuramycins to enhance antibacterial activity.

ABSTRACT:

Objectives

To extend capuramycin spectrum of activity beyond mycobacteria and improve intracellular drug activity.

Methods

Three capuramycin analogues (SQ997, SQ922 and SQ641) were conjugated with different natural and unnatural amino acids or decanoic acid (DEC) through an ester bond at one or more available hydroxyl groups. In vitro activity of the modified compounds was determined against Mycobacterium spp. and representative Gram-positive and Gram-negative bacteria. Intracellular activity was evaluated in J774A.1 mouse macrophages infected with Mycobacterium tuberculosis (H37Rv).

Results

Acylation of SQ997 and SQ641 with amino undecanoic acid (AUA) improved in vitro activity against most of the bacteria tested. Conjugation of SQ922 with DEC, but not AUA, improved

SUBMITTER: Bogatcheva E 

PROVIDER: S-EPMC3037154 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature