Abstract
A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by Streptomyces pactum ATCC 27456. The fluorinated compounds maintain excellent activity and selectivity toward chloroquine-sensitive and multidrug-resistant strains of malarial parasites as the parent compounds. The results also provide insights into the biosynthesis of 3-aminobenzoic acid in S. pactum.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Antimalarials / chemical synthesis*
-
Antimalarials / chemistry
-
Antimalarials / pharmacology*
-
Chloroquine / pharmacology
-
Drug Resistance / drug effects
-
Drug Resistance, Multiple / drug effects
-
Hydrocarbons, Fluorinated / chemical synthesis*
-
Hydrocarbons, Fluorinated / chemistry
-
Hydrocarbons, Fluorinated / pharmacology*
-
Molecular Structure
-
Pactamycin / analogs & derivatives*
-
Pactamycin / chemical synthesis*
-
Pactamycin / chemistry
-
Pactamycin / pharmacology*
-
Plasmodium falciparum / drug effects
-
Streptomyces / chemistry
-
Streptomyces / genetics
-
Streptomyces / metabolism
-
meta-Aminobenzoates
Substances
-
Antimalarials
-
Hydrocarbons, Fluorinated
-
TM-025
-
TM-026
-
meta-Aminobenzoates
-
Pactamycin
-
Chloroquine
-
3-aminobenzoic acid