Evaluation of pseudopteroxazole and pseudopterosin derivatives against Mycobacterium tuberculosis and other pathogens.

Abstract

Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for in vitro antimicrobial and cytotoxic activities. A number of congeners exhibited antimicrobial activity against a range of Gram-positive bacteria including Mycobacterium tuberculosis H₃₇Rv, with four displaying notable antitubercular activity against both replicating and non-replicating persistent forms of M. tuberculosis. One new semi-synthetic compound, 21-((1H-imidazol-5-yl)methyl)-pseudopteroxazole (7a), was more potent than the natural products pseudopterosin and pseudopteroxazole and exhibited equipotent activity against both replicating and non-replicating persistent forms of M.tuberculosis with a near absence of in vitro cytotoxicity. Pseudopteroxazole also exhibited activity against strains of M. tuberculosis H₃₇Rv resistant to six clinically used antibiotics.

• Authors: Malcolm W B McCulloch, Brad Haltli, Douglas H Marchbank, Russell G Kerr
• Journal: Marine drugs (Mar Drugs) Vol. 10 Issue 8 Pg. 1711-1728 (Aug 2012) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 23015770 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antitubercular Agents
• Diterpenes
• Glycosides
• Oxazoles
• pseudopterosins
• pseudopteroxazole

Topics

• Animals
• Anti-Bacterial Agents (chemistry, pharmacology, toxicity)
• Antitubercular Agents (chemistry, pharmacology, toxicity)
• Chlorocebus aethiops
• Diterpenes (chemistry, pharmacology, toxicity)
• Drug Resistance, Multiple, Bacterial
• Glycosides (chemistry, pharmacology, toxicity)
• Gram-Positive Bacteria (drug effects)
• Microbial Sensitivity Tests
• Mycobacterium tuberculosis (drug effects)
• Oxazoles (chemistry, pharmacology, toxicity)
• Structure-Activity Relationship
• Toxicity Tests
• Vero Cells