Novel Isoniazid-Carborane Hybrids Active in Vitro Against Mycobacterium tuberculosis
| Autor: | Anna Żaczek, Dorota Gurda, Jarosław Dziadek, Daria Różycka, Małgorzata Korycka-Machała, Wojciech Rypniewski, Marta Orlicka-Płocka, Agnieszka B. Olejniczak, Eliza Wyszko, Katarzyna Biniek-Antosiak |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
isoniazid Tuberculosis Mutant Pharmaceutical Science lcsh:Medicine lcsh:RS1-441 antitubercular activity 01 natural sciences Microbiology Mycobacterium tuberculosis lcsh:Pharmacy and materia medica 03 medical and health sciences Minimum inhibitory concentration carborane Drug Discovery medicine biology 010405 organic chemistry Chemistry Isoniazid High mortality lcsh:R medicine.disease biology.organism_classification bacterial infections and mycoses In vitro 0104 chemical sciences boron cluster 030104 developmental biology Molecular Medicine Carborane medicine.drug |
| Zdroj: | Pharmaceuticals, Vol 13, Iss 465, p 465 (2020) Pharmaceuticals Volume 13 Issue 12 |
| ISSN: | 1424-8247 |
| Popis: | Tuberculosis (TB) is a severe infectious disease with high mortality and morbidity. The emergence of drug-resistant TB has increased the challenge to eliminate this disease. Isoniazid (INH) remains the key and effective component in the therapeutic regimen recommended by World Health Organization (WHO). A series of isoniazid-carborane derivatives containing 1,2-dicarba-closo-dodecaborane, 1,7-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, or 7,8-dicarba-nido-undecaborate anion were synthesized for the first time. The compounds were tested in vitro against the Mycobacterium tuberculosis (Mtb) H37Rv strain and its mutant (DkatG) defective in the synthesis of catalase-peroxidase (KatG). N&prime ((7,8-dicarba-nido-undecaboranyl)methylidene)isonicotinohydrazide (16) showed the highest activity against the wild-type Mtb strain. All hybrids could inhibit the growth of the &Delta katG mutant in lower concentrations than INH. N&prime ([(1,12-dicarba-closo-dodecaboran-1yl)ethyl)isonicotinohydrazide (25) exhibited more than 60-fold increase in activity against Mtb DkatG as compared to INH. This compound was also found to be noncytotoxic up to a concentration four times higher than the minimum inhibitory concentration 99% (MIC99) value. |
| Databáze: | OpenAIRE |
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