title: Design, synthesis, and application of novel triclosan prodrugs as potential antimalarial and antibacterial agents.
abstract: A number of new triclosan-conjugated analogs bearing biodegradable ester linkage have been synthesized, characterized and evaluated for their antimalarial and antibacterial activities. Many of these compounds exhibit good inhibition against Plasmodium falciparum and Escherichia coli. Among them tertiary amine containing triclosan-conjugated prodrug (5) inhibited both P. falciparum (IC(50); 0.62microM) and E. coli (IC(50); 0.26microM) at lower concentrations as compared to triclosan. Owing to the presence of a cleavable ester moiety, these new prodrugs are hydrolyzed under physiological conditions and parent molecule, triclosan, is released. Further, introduction of tertiary/quaternary functionality increases their cellular uptake. These properties impart them with higher potency to their antimalarial as well as antibacterial activities. The best compound among them 5 shows close to four-fold enhanced activities against P. falciparum and E. coli cultures as compared to triclosan.
authors.affiliation: Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India.
authors.forename: Satyendra
authors.initials: S
authors.lastname: Mishra
authors.forename: Krishanpal
authors.initials: K
authors.lastname: Karmodiya
authors.forename: Prasanna
authors.initials: P
authors.lastname: Parasuraman
authors.forename: Avadhesha
authors.initials: A
authors.lastname: Surolia
authors.forename: Namita
authors.initials: N
authors.lastname: Surolia
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors; D014260:Triclosan / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000962:Antimalarials; D011355:Prodrugs; D014260:Triclosan