Development of multi-drug resistance (MDR) bacteria in the past five decades have led to increasing research in search of a drug candidate to address this AMR issue. A fully synthetic broad-spectrum antibiotic, Iboxamycin, provides hope to treat both Gram-positive and Gram-negative bacteria via a bacteriostatic mechanism.
Skupina linkozamida antibiotici comprising particularly of clindamycin is a safe common antibiotik available orally. It is a bacteriostatic agent and acts by binding to bacterial ribosomes. Lincomycin, the first antibiotik of this group was isolated from soil bacteria Streptomyces lincolnensis 1963. i upotrijebljen protiv gram pozitivnih bakterija.
Clindamycin, the semi-synthetic version of lincomycin has been in use for the last 50 years as an antibacterial (and antimalarial drug), particularly for the treatment of dental and bone infections. Because of its widespread use for about five decades, multiple resistance genes have now evolved, making clindamycin less effective against several bacteria in the community. Also, no other antibiotik in this group saw light of the day despite hard efforts in the past few decades.
Istraživači su nedavno izvijestili o kemijskoj sintezi iboksamicina (IBX), novog linkozamida za koji je utvrđeno da je vrlo učinkovit protiv gram-pozitivnih i gram-negativnih bakterija u vitro i in vivo animal studies. Through structure-based design and component-based synthesis, they developed a scaffold and linked that to the amino-octose residue of clindamycin. The result is Iboxamycin, an antibiotik which has been found to be exceptionally potent against a wide range of pathogenic bacteria in pre-clinical studies on mice. It targets wild-type and resistant bacteria and exhibits prolonged bacteriostatic effects following even brief exposure.
Development of this broad-spectrum antibiotik candidate is very significant in the current times, when commonly used antibiotici have increasingly lost shine due to evolution of multiple drug-resistance (MDR), caused mainly as a result of indiscriminate use of antibiotici, čineći tako antibiotik resistance a serious threat to global health.
Osim toga, za razliku od linkomicina i klindamicina koji su prirodni, odnosno polusintetski, novorazvijeni kandidat Iboxamycin (IBX) je potpuno sintetski, što znači da njegova dostupnost možda neće u potpunosti ovisiti o prirodnim izvorima, pa bi se stoga njegova industrijska proizvodnja lako mogla povećati da zadovolji veće zahtjeve. Također, moguća je i sinteza nekoliko analoga jer se proces temelji na komponentama. Daljnji dokazi njegove učinkovitosti i sigurnosti bit će dostupni nakon pokretanja kliničkih ispitivanja, što će se dogoditi samo kada se farmaceutska industrija uključi i dobije patentna prava od izumitelja, kako bi se dalje proširila.
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Izvori:
- Mitcheltree, MJ, Pisipati, A., Syroegin, EA i sur. Klasa sintetičkih antibiotika koja prevladava otpornost bakterija na više lijekova. Objavljeno: 27. listopada 2021. Priroda (2021.). DOI: https://doi.org/10.1038/s41586-021-04045-6
- Mason J., et al. 2021. Praktična sinteza iboksamicina na gramskoj skali, snažnog kandidata za antibiotike. J. Am. Chem. Soc. 2021, 143, 29, 11019–11025. Datum objave: 15. srpnja 2021. DOI: https://doi.org/10.1021/jacs.1c03529 Dostupno na link
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