| Identifikační kód |
RIV/00216208:11160/22:10451164 |
| Název v anglickém jazyce |
Improving Antimicrobial Activity and Physico-Chemical Properties by Isosteric Replacement of 2-Aminothiazole with 2-Aminooxazole |
| Druh |
J - Recenzovaný odborný článek (Jimp, Jsc a Jost) |
| Poddruh |
J/A - Článek v odborném periodiku je obsažen v databázi Web of Science společností Thomson Reuters s příznakem „Article“, „Review“ nebo „Letter“ (Jimp) |
| Jazyk |
eng - angličtina |
| Vědní obor |
30104 - Pharmacology and pharmacy |
| Rok uplatnění |
2022 |
| Kód důvěrnosti údajů |
S - Úplné a pravdivé údaje o výsledku nepodléhající ochraně podle zvláštních právních předpisů. |
| Počet výskytů výsledku |
4 |
| Popis výsledku v anglickém jazyce |
Antimicrobial drug resistance is currently one of the most critical health issues. Pathogens resistant to last-resort antibiotics are increasing, and very few effective antibacterial agents have been introduced in recent years. The promising drug candidates are often discontinued in the primary stages of the drug discovery pipeline due to their unspecific reactivity (PAINS), toxicity, insufficient stability, or low water solubility. In this work, we investigated a series of substituted N-oxazolyl-and N-thiazolylcarboxamides of various pyridinecarboxylic acids. Final compounds were tested against several microbial species. In general, oxazole-containing compounds showed high activity against mycobacteria, especially Mycobacterium tuberculosis (best MIC(H37Ra) = 3.13 mu g/mL), including the multidrug-resistant strains. Promising activities against various bacterial and fungal strains were also observed. None of the compounds was significantly cytotoxic against the HepG2 cell line. Experimental measurement of lipophilicity parameter log k'(w) and water solubility (log S) confirmed significantly (typically two orders in logarithmic scale) increased hydrophilicity/water solubility of oxazole derivatives in comparison with their thiazole isosteres. Mycobacterial beta-ketoacyl-acyl carrier protein synthase III (FabH) was suggested as a probable target by molecular docking and molecular dynamics simulations. |
| Klíčová slova oddělená středníkem |
water solubility;pyridine;isostere;molecular dynamics;molecular docking;docking;antimycobacterial activity;aminothiazole;aminooxazole |
| Stránka www, na které se nachází výsledek |
https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=NmRZiUw9Qa |
| DOI výsledku |
10.3390/ph15050580 |
| Odkaz na údaje z výzkumu |
- |