Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives
Abstract Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv Mycobacterium tuberculosis( M. tb) strain. CPF derivative16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. tb DNA gyrase. Isoniazid‐pyrazinoic acid (INH‐POA) hybrid21a showed the highest potency in our study (MIC = 2 µg/ml). It also retained its high activity against the other tested M. tb drug‐sensitive strain (DS) V4207 (MIC = 4 µg/ml) and demonstrated negligible cytotoxicity against Vero cells (IC50 ≥ 64 µg/ml). Four tested drug‐resistant (DR) M. tb strains were refractory to21a, similar to INH, whilst being sensitive to CPF. Compound21a was also inactive against two non‐tuberculous mycobacterial (NTM) strains, suggesting its selective activity against M. tb. The noteworthy activity of21a against DS strains and its low cytotoxicity highlight its potential to treat DS M. tb..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
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| Enthalten in: |
Chemical Biology & Drug Design - 97(2021), 6, Seite 1137-1150 |
| Beteiligte Personen: |
Alsayed, Shahinda S. R. [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
Copyright © 2021 John Wiley & Sons A/S |
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| Umfang: |
14 |
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| doi: |
10.1111/cbdd.13836 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Abstract Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv Mycobacterium tuberculosis( M. tb) strain. CPF derivative16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. tb DNA gyrase. Isoniazid‐pyrazinoic acid (INH‐POA) hybrid21a showed the highest potency in our study (MIC = 2 µg/ml). It also retained its high activity against the other tested M. tb drug‐sensitive strain (DS) V4207 (MIC = 4 µg/ml) and demonstrated negligible cytotoxicity against Vero cells (IC50 ≥ 64 µg/ml). Four tested drug‐resistant (DR) M. tb strains were refractory to21a, similar to INH, whilst being sensitive to CPF. Compound21a was also inactive against two non‐tuberculous mycobacterial (NTM) strains, suggesting its selective activity against M. tb. The noteworthy activity of21a against DS strains and its low cytotoxicity highlight its potential to treat DS M. tb. | ||
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