Aspects of the antituberculous activity of 27753-RP, a new semisynthetic derivative of griselimycine

Looking Back to the Future: Predicting in Vivo Efficacy of Small Molecules versus Mycobacterium tuberculosis

“…For example, after testing in mice, it was suggested that 27753-RP was a highly promising antituberculosis drug. 80 Subsequently, in the absence of supportive data, it was stated that griselimycin(e) while effective in vitro against Mtb was inactive in vivo . We were unable to find any further information on these compounds in the literature beyond their structures.…”

Biosynthetic Pathways to Nonproteinogenic α-Amino Acids

“…133 The griselimycins disrupt DNA replication using a novel mechanism and are effective against resistant strains of Mycobacterium tuberculosis. 134 Methylgriselimycin (78) (Figure 16), with a 69 residue at position 8, was found to have increased metabolic stability when compared to griselimycin, resulting in improved efficacy against M. tuberculosis. 135 To better understand the biosynthesis of 69, the Muller group sequenced the griselimycin producer S. muensis DSM 40835, identifying the biosynthetic gene cluster.…”

Biosynthesis of methyl-proline containing griselimycins, natural products with anti-tuberculosis activity

“…1 ) isolated from the Streptomyces strain DSM 40835, were reported as effective against drug-resistant M. tuberculosis in the 1960s, but their development was abandoned due to their poor pharmacokinetic properties. 2 – 6 In a re-assessment of GMs, we have recently shown that GMs target DnaN, the sliding clamp of DNA-polymerase, thereby circumventing common forms of TB drug resistance. 7 To improve the in vivo properties of GMs, we searched for metabolically labile sites and found that degradation starting with the oxidation of proline at position 8 of the GM was a major issue.…”