SQ109 and PNU-100480 interact to kill Mycobacterium tuberculosis in vitro.

Objectives: To investigate in vitro interaction between two compounds, SQ109 and PNU-100480, currently in development for the treatment of Mycobacterium tuberculosis (MTB).

Methods: The two-drug interactions between SQ109 and PNU-100480 and its major metabolite PNU-101603 were assessed by chequerboard titration, and the rate of killing and intracellular activity were determined in both J774A.1 mouse macrophages and whole blood culture.

Chemical modification of capuramycins to enhance antibacterial activity.

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.

In vitro antimicrobial activities of capuramycin analogues against non-tuberculous mycobacteria.

Objectives: To determine antibacterial activity of capuramycin analogues SQ997, SQ922, SQ641 and RKS2244 against several non-tuberculous mycobacteria (NTM).

Methods: In vitro antibiotic activities, i.e.