Naslov
Prediction of environmental microbial biotransformation of azithromycin, its thiosemicarbazone conjugates and their precursors

Autori
Takač, Tin ; Jadrijević-Mladar Takač, Milena ; Jednačak, Tomislav

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
28th Croatian Meeting of Chemists and Chemical Engineers: Book of Abstracts / Rogošić, Marko - Zagreb : Hrvatsko društvo kemijskih inženjera i tehnologa (HDKI), 2023, 242-242

Skup
28th Croatian Meeting of Chemists and Chemical Engineers

Mjesto i datum
Rovinj, Hrvatska, 28.03.2023. - 31.03.2023

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
macrolide antibiotics, azithromycin, macrozones, environmental microbial biotransformation, bioavailability, in silico

Sažetak
Antibiotics and their derivatives are often contaminants of soils and waters, and once released into the environment, they are further degraded by soil and/or aquatic microbes, thus contributing to antimicrobial resistance (AMR). To date, most studies have focused on the parent molecule and paid little attention to the metabolites they produce, the characterization of which is critical as they may also contribute to AMR. [1] In this work, the biotransformation products of azithromycin (AZI) and its thiosemicarbazone conjugates (macrozones) MZ–9a, MZ–4’’, and MZ–3 were evaluated using BioTransformer, a web tool for predicting metabolite and degradation products by environmental microbes (www.biotransformer.ca). [2] The results of this study showed that regardless of the position of the thiosemicarbazone moiety (either at 9a, 4’’, or 3) in the azithromycin molecule, the predicted sites for biotransformations were at C1, C3, C5, C11, and C13 in the macrolide ring, C2’, C3’’, and C4’’ in sugars, while in the thiosemicarbazone moiety, the amide and C=S functional groups are to be biotransformed. The reactions include oxidation of the secondary alcohol groups at C2’, C4’’, and C11, hydrolysis of the lactone ring, glycosidic bond at C3 and C5 and amide, and sulfoxidation of S atom in macrozones. The predicted metabolites were evaluated using SwissADME, a free web tool for assessing the pharmacokinetics and drug- likeness of small molecules (www.swissadme.ch). [3] According to the bioavailability radars obtained, that enable a first glance at the drug- likeness of a molecule, those metabolites still consist of a macrolide ring, i.e., the synthetic macrozone precursors 9a-, 4’’- or 3-aminopropyl azithromycin, and their 9a̶̶-, 4’’- or 3-O- dealkylated metabolites exhibited the best bioavailability properties.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Interdisciplinarne prirodne znanosti, Farmacija

POVEZANOST RADA