Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives
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....
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| Format: | Journal Article |
| Language: | English |
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WILEY
2021
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| Online Access: | http://purl.org/au-research/grants/arc/DE160100482 http://hdl.handle.net/20.500.11937/90990 |
| _version_ | 1848765479464730624 |
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| author | Alsayed, Shahinda S.R. Lun, S. Payne, Alan Bishai, William R. Gunosewoyo, Hendra |
| author_facet | Alsayed, Shahinda S.R. Lun, S. Payne, Alan Bishai, William R. Gunosewoyo, Hendra |
| author_sort | Alsayed, Shahinda S.R. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T11:35:54Z |
| format | Journal Article |
| id | curtin-20.500.11937-90990 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:35:54Z |
| publishDate | 2021 |
| publisher | WILEY |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-909902023-05-24T01:28:51Z Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives Alsayed, Shahinda S.R. Lun, S. Payne, Alan Bishai, William R. Gunosewoyo, Hendra Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Chemistry, Medicinal Pharmacology & Pharmacy ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis Animals Antitubercular Agents Binding Sites Catalytic Domain Cell Survival Chlorocebus aethiops Ciprofloxacin DNA Gyrase Drug Design Drug Resistance, Bacterial Isoniazid Microbial Sensitivity Tests Molecular Conformation Molecular Docking Simulation Mycobacterium tuberculosis Nontuberculous Mycobacteria Pyrazinamide Structure-Activity Relationship Vero Cells Vero Cells Animals Mycobacterium tuberculosis Isoniazid Pyrazinamide Ciprofloxacin DNA Gyrase Antitubercular Agents Microbial Sensitivity Tests Drug Resistance, Bacterial Cell Survival Binding Sites Catalytic Domain Molecular Conformation Structure-Activity Relationship Drug Design Nontuberculous Mycobacteria Molecular Docking Simulation Chlorocebus aethiops 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. 2021 Journal Article http://hdl.handle.net/20.500.11937/90990 10.1111/cbdd.13836 English http://purl.org/au-research/grants/arc/DE160100482 WILEY fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Chemistry, Medicinal Pharmacology & Pharmacy ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis Animals Antitubercular Agents Binding Sites Catalytic Domain Cell Survival Chlorocebus aethiops Ciprofloxacin DNA Gyrase Drug Design Drug Resistance, Bacterial Isoniazid Microbial Sensitivity Tests Molecular Conformation Molecular Docking Simulation Mycobacterium tuberculosis Nontuberculous Mycobacteria Pyrazinamide Structure-Activity Relationship Vero Cells Vero Cells Animals Mycobacterium tuberculosis Isoniazid Pyrazinamide Ciprofloxacin DNA Gyrase Antitubercular Agents Microbial Sensitivity Tests Drug Resistance, Bacterial Cell Survival Binding Sites Catalytic Domain Molecular Conformation Structure-Activity Relationship Drug Design Nontuberculous Mycobacteria Molecular Docking Simulation Chlorocebus aethiops Alsayed, Shahinda S.R. Lun, S. Payne, Alan Bishai, William R. Gunosewoyo, Hendra Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title | Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title_full | Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title_fullStr | Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title_full_unstemmed | Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title_short | Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| title_sort | facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives |
| topic | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology Chemistry, Medicinal Pharmacology & Pharmacy ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis ciprofloxacin hybrid molecules indoleamides isoniazid pyrazinamide tuberculosis Animals Antitubercular Agents Binding Sites Catalytic Domain Cell Survival Chlorocebus aethiops Ciprofloxacin DNA Gyrase Drug Design Drug Resistance, Bacterial Isoniazid Microbial Sensitivity Tests Molecular Conformation Molecular Docking Simulation Mycobacterium tuberculosis Nontuberculous Mycobacteria Pyrazinamide Structure-Activity Relationship Vero Cells Vero Cells Animals Mycobacterium tuberculosis Isoniazid Pyrazinamide Ciprofloxacin DNA Gyrase Antitubercular Agents Microbial Sensitivity Tests Drug Resistance, Bacterial Cell Survival Binding Sites Catalytic Domain Molecular Conformation Structure-Activity Relationship Drug Design Nontuberculous Mycobacteria Molecular Docking Simulation Chlorocebus aethiops |
| url | http://purl.org/au-research/grants/arc/DE160100482 http://hdl.handle.net/20.500.11937/90990 |