Synthesis and Activity of a Novel Class of Tribasic Macrocyclic Antibiotics: The Triamilides

Macrolide resistance mechanisms inEnterobacteriaceae: Focus on azithromycin

“…Regarding structural modifications, four different classes have been described: those classically referred to as macrolides, such as erythromycin, which were the molecules first described; azalides, like azithromycin, that incorporate a nitrogen in the macrolactonic ring resulting in higher basicity and increasing both acid stability and bioavailability (Mutak, 2007); and ketolides, which possess a keto group at the C3 position of the lactone ring instead of the cladinose sugar found in erythromycin, enhancing their activity spectrum and improving their acid stability, and of which telithromycin is a representative class member (Ackermann & Rodloff, 2003;Schl€ unzen et al, 2003;Zhanel et al, 2002); finally, ketolides such as solithromycin, which incorporate a fluor atom in C2 (fluoroketolides), are currently under development (Llano-Sotelo et al, 2010;Putnam et al, 2010). Additionally, subclasses such as triamilides, which are represented by tulatrhomycin, a tribasic derivative azalide, have also been proposed (Letavic et al, 2002). Other classifications proposed are based on generations or mean plasma elimination half-life; thus, four generations are considered, with erythromycin representing the first, leucomycin the second, azithromycin the third and telithromycin the fourth (Morar et al, 2012).…”

Pharmacokinetics of Tulathromycin in Healthy and Neutropenic Mice Challenged Intranasally with Lipopolysaccharide from Escherichia coli

“…However, the identification and description of the mechanism(s) involved in tulathromycin lung tissue accumulation still remain unknown. Tulathromycin is a lipid-soluble triamilide (15). Therefore, the overall molecule contains three basic functional groups with pK a values ranging from 8.6 to 9.9.…”

“…It represents the first member of a novel subclass of macrolides known as triamilides (15). This macrolide shows metaphylactic and therapeutic efficacy in bovine and swine respiratory disease after a single administration (20,23).…”

Pharmacokinetics of tulathromycin in edible tissues of healthy and experimentally infected pigs withActinobacillus pleuropneumoniae

“…Tulathromycin is a semi-synthetic triamilide, broad spectrum antimicrobial agent, which belongs to the macrolide group of antibiotics. Triamililides favourable tissue distribution and half-life as well as their broad-spectrum antimicrobial are related to the 15-membered azalides ring (Letavic et al 2002). Although all macrolides are basic molecules with dissociation constant (pKa) higher than 7, the tulathromycin molecule is more basic than other macrolides.…”