Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives
© 2021 John Wiley & Sons Ltd..
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 derivative 16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. tb DNA gyrase. Isoniazid-pyrazinoic acid (INH-POA) hybrid 21a 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 to 21a, similar to INH, whilst being sensitive to CPF. Compound 21a was also inactive against two non-tuberculous mycobacterial (NTM) strains, suggesting its selective activity against M. tb. The noteworthy activity of 21a against DS strains and its low cytotoxicity highlight its potential to treat DS M. tb.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:97 |
|---|---|
| Enthalten in: |
Chemical biology & drug design - 97(2021), 6 vom: 01. Juni, Seite 1137-1150 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Alsayed, Shahinda S R [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 19.11.2021 Date Revised 02.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1111/cbdd.13836 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM321963741 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM321963741 | ||
| 003 | DE-627 | ||
| 005 | 20240402232523.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/cbdd.13836 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1360.xml |
| 035 | |a (DE-627)NLM321963741 | ||
| 035 | |a (NLM)33638304 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Alsayed, Shahinda S R |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.11.2021 | ||
| 500 | |a Date Revised 02.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2021 John Wiley & Sons Ltd. | ||
| 520 | |a 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 derivative 16 displayed a modest activity (MIC = 16 µg/ml) and was docked into the M. tb DNA gyrase. Isoniazid-pyrazinoic acid (INH-POA) hybrid 21a 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 to 21a, similar to INH, whilst being sensitive to CPF. Compound 21a was also inactive against two non-tuberculous mycobacterial (NTM) strains, suggesting its selective activity against M. tb. The noteworthy activity of 21a against DS strains and its low cytotoxicity highlight its potential to treat DS M. tb | ||
| 650 | 4 | |a Letter | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a ciprofloxacin | |
| 650 | 4 | |a hybrid molecules | |
| 650 | 4 | |a indoleamides | |
| 650 | 4 | |a isoniazid | |
| 650 | 4 | |a pyrazinamide | |
| 650 | 4 | |a tuberculosis | |
| 650 | 7 | |a Antitubercular Agents |2 NLM | |
| 650 | 7 | |a Pyrazinamide |2 NLM | |
| 650 | 7 | |a 2KNI5N06TI |2 NLM | |
| 650 | 7 | |a Ciprofloxacin |2 NLM | |
| 650 | 7 | |a 5E8K9I0O4U |2 NLM | |
| 650 | 7 | |a DNA Gyrase |2 NLM | |
| 650 | 7 | |a EC 5.99.1.3 |2 NLM | |
| 650 | 7 | |a Isoniazid |2 NLM | |
| 650 | 7 | |a V83O1VOZ8L |2 NLM | |
| 700 | 1 | |a Lun, Shichun |e verfasserin |4 aut | |
| 700 | 1 | |a Payne, Alan |e verfasserin |4 aut | |
| 700 | 1 | |a Bishai, William R |e verfasserin |4 aut | |
| 700 | 1 | |a Gunosewoyo, Hendra |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Chemical biology & drug design |d 2006 |g 97(2021), 6 vom: 01. Juni, Seite 1137-1150 |w (DE-627)NLM160848377 |x 1747-0285 |7 nnns |
| 773 | 1 | 8 | |g volume:97 |g year:2021 |g number:6 |g day:01 |g month:06 |g pages:1137-1150 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/cbdd.13836 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 97 |j 2021 |e 6 |b 01 |c 06 |h 1137-1150 | ||