Sulfone and phosphinic acid analogs of decaprenolphosphoarabinose as potential anti-tuberculosis agents.

Abstract

Mycobacteria biosynthesize a cell wall structure that is rich in polysaccharides containing arabinofuranose residues. The source of these arabinofuranose residues is decaprenolphosphoarabinose (1), the donor substrate for mycobacterial arabinosyltransferases. We have previously demonstrated that an analog of 1, C-phosphonate 7, prevented the growth of mycobacteria and this compound is currently undergoing testing for efficacy in tuberculosis-infected mice. We describe here the synthesis and testing of additional analogs of 1 that contain either a sulfone (8-14) or phosphinic acid (15-19) moiety in place of the phosphodiester functionality. Screening of these compounds in vitro against Mycobacterium tuberculosis strain H(37)Rv revealed that while some of these compounds possessed low to modest activity, none was as potent as 7.

• Authors: Charla A Centrone, Todd L Lowary
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 12 Issue 21 Pg. 5495-503 (Nov 01 2004) ISSN: 0968-0896 [Print] England
• PMID: 15465326 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antitubercular Agents
• Galactans
• Hemiterpenes
• Lipopolysaccharides
• Pentanols
• Phosphinic Acids
• Sulfonic Acids
• lipoarabinomannan
• prenol
• Arabinose
• arabinogalactan

Topics

• Antitubercular Agents (chemistry, pharmacology)
• Arabinose (analogs & derivatives, pharmacology)
• Galactans (chemistry)
• Hemiterpenes
• Lipopolysaccharides (chemistry)
• Mycobacterium tuberculosis (drug effects)
• Pentanols (chemistry, pharmacology)
• Phosphinic Acids (chemistry, pharmacology)
• Sulfonic Acids (chemistry, pharmacology)