Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens
Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the ter...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2012-08-01
|
| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1660-3397/10/8/1711 |
| _version_ | 1811183949624377344 |
|---|---|
| author | Malcolm W. B. McCulloch Brad Haltli Douglas H. Marchbank Russell G. Kerr |
| author_facet | Malcolm W. B. McCulloch Brad Haltli Douglas H. Marchbank Russell G. Kerr |
| author_sort | Malcolm W. B. McCulloch |
| collection | DOAJ |
| description | Pseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for <em>in</em> <em>vitro</em> antimicrobial and cytotoxic activities. A number of congeners exhibited antimicrobial activity against a range of Gram-positive bacteria including <em>Mycobacterium</em> <em>tuberculosis</em> H<sub>37</sub>Rv, with four displaying notable antitubercular activity against both replicating and non-replicating persistent forms of <em>M.</em> <em>tuberculosis</em>. One new semi-synthetic compound, 21-((1<em>H</em>-imidazol-5-yl)methyl)-pseudopteroxazole (<strong>7a</strong>), was more potent than the natural products pseudopterosin and pseudopteroxazole and exhibited equipotent activity against both replicating and non-replicating persistent forms of <em>M.</em> <em>tuberculosis</em> with a near absence of <em>in</em> <em>vitro</em> cytotoxicity. Pseudopteroxazole also exhibited activity against strains of <em>M.</em> <em>tuberculosis</em> H<sub>37</sub>Rv resistant to six clinically used antibiotics. |
| first_indexed | 2024-04-11T13:05:14Z |
| format | Article |
| id | doaj.art-a4679633c42d41b7b639d8e48ae0a639 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:05:14Z |
| publishDate | 2012-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-a4679633c42d41b7b639d8e48ae0a6392022-12-22T04:22:47ZengMDPI AGMarine Drugs1660-33972012-08-011081711172810.3390/md10081711Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other PathogensMalcolm W. B. McCullochBrad HaltliDouglas H. MarchbankRussell G. KerrPseudopterosins and pseudopteroxazole are intriguing marine natural products that possess notable antimicrobial activity with a commensurate lack of cytotoxicity. New semi-synthetic pseudopteroxazoles, pseudopteroquinoxalines and pseudopterosin congeners along with simple synthetic mimics of the terpene skeleton were synthesized. In order to build structure-activity relationships, a set of 29 new and previously reported compounds was assessed for <em>in</em> <em>vitro</em> antimicrobial and cytotoxic activities. A number of congeners exhibited antimicrobial activity against a range of Gram-positive bacteria including <em>Mycobacterium</em> <em>tuberculosis</em> H<sub>37</sub>Rv, with four displaying notable antitubercular activity against both replicating and non-replicating persistent forms of <em>M.</em> <em>tuberculosis</em>. One new semi-synthetic compound, 21-((1<em>H</em>-imidazol-5-yl)methyl)-pseudopteroxazole (<strong>7a</strong>), was more potent than the natural products pseudopterosin and pseudopteroxazole and exhibited equipotent activity against both replicating and non-replicating persistent forms of <em>M.</em> <em>tuberculosis</em> with a near absence of <em>in</em> <em>vitro</em> cytotoxicity. Pseudopteroxazole also exhibited activity against strains of <em>M.</em> <em>tuberculosis</em> H<sub>37</sub>Rv resistant to six clinically used antibiotics.http://www.mdpi.com/1660-3397/10/8/1711pseudopteroxazolessemi-synthesis<em>Mycobacterium</em> <em>tuberculosis</em>antibiotic-resistance |
| spellingShingle | Malcolm W. B. McCulloch Brad Haltli Douglas H. Marchbank Russell G. Kerr Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens Marine Drugs pseudopteroxazoles semi-synthesis <em>Mycobacterium</em> <em>tuberculosis</em> antibiotic-resistance |
| title | Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens |
| title_full | Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens |
| title_fullStr | Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens |
| title_full_unstemmed | Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens |
| title_short | Evaluation of Pseudopteroxazole and Pseudopterosin Derivatives against <em>Mycobacterium</em> <em>tuberculosis</em> and Other Pathogens |
| title_sort | evaluation of pseudopteroxazole and pseudopterosin derivatives against lt em gt mycobacterium lt em gt lt em gt tuberculosis lt em gt and other pathogens |
| topic | pseudopteroxazoles semi-synthesis <em>Mycobacterium</em> <em>tuberculosis</em> antibiotic-resistance |
| url | http://www.mdpi.com/1660-3397/10/8/1711 |
| work_keys_str_mv | AT malcolmwbmcculloch evaluationofpseudopteroxazoleandpseudopterosinderivativesagainstltemgtmycobacteriumltemgtltemgttuberculosisltemgtandotherpathogens AT bradhaltli evaluationofpseudopteroxazoleandpseudopterosinderivativesagainstltemgtmycobacteriumltemgtltemgttuberculosisltemgtandotherpathogens AT douglashmarchbank evaluationofpseudopteroxazoleandpseudopterosinderivativesagainstltemgtmycobacteriumltemgtltemgttuberculosisltemgtandotherpathogens AT russellgkerr evaluationofpseudopteroxazoleandpseudopterosinderivativesagainstltemgtmycobacteriumltemgtltemgttuberculosisltemgtandotherpathogens |