Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin
Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compa...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2016.1261129 |
| _version_ | 1818924798447714304 |
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| author | Gennady B. Lapa Elena P. Mirchink Elena B Isakova Maria N Preobrazhenskaya |
| author_facet | Gennady B. Lapa Elena P. Mirchink Elena B Isakova Maria N Preobrazhenskaya |
| author_sort | Gennady B. Lapa |
| collection | DOAJ |
| description | Clarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone’s cycle via oxime linker, the second direction used the modification of the 4″-O-group of cladinose via the formation of carbamates of benzoxaboroles. 4″-O-(3-S-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborole)-methyl-carbamoyl-clarithromycin showed twofold decrease in MICs for S. epidermidis and S. pneumoniae than clarithromycin. 4″-O-Modified clarithromycin demonstrated an efficacy against Gram positive strains only. Compounds with C-9 substitution were more active than 4″-O-substituted antibiotics for susceptible strains E. coli tolC and did not exceed the activity of initial antibiotics. |
| first_indexed | 2024-12-20T02:31:03Z |
| format | Article |
| id | doaj.art-336b7b43de07490193e53c3207d4d1cb |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-20T02:31:03Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-336b7b43de07490193e53c3207d4d1cb2022-12-21T19:56:34ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742017-01-0132145245610.1080/14756366.2016.12611291261129Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycinGennady B. Lapa0Elena P. Mirchink1Elena B Isakova2Maria N Preobrazhenskaya3Blokhin Cancer CenterGause Institute of New AntibioticsGause Institute of New AntibioticsGause Institute of New AntibioticsClarithromycin (active against Gram positive infections) and 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole derivatives (effective for Gram negative microbes) are the ligands of bacterial RNA. The antimicrobial activities of these benzoxaboroles linked with clarithromycin at 9 or 4″ position were compared. Two synthetic pathways for these conjugates were elaborated. First pathway explored the substitution of the C-9 carbonyl group of macrolactone’s cycle via oxime linker, the second direction used the modification of the 4″-O-group of cladinose via the formation of carbamates of benzoxaboroles. 4″-O-(3-S-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborole)-methyl-carbamoyl-clarithromycin showed twofold decrease in MICs for S. epidermidis and S. pneumoniae than clarithromycin. 4″-O-Modified clarithromycin demonstrated an efficacy against Gram positive strains only. Compounds with C-9 substitution were more active than 4″-O-substituted antibiotics for susceptible strains E. coli tolC and did not exceed the activity of initial antibiotics.http://dx.doi.org/10.1080/14756366.2016.1261129Antibioticmacrolactonemacrolideclarithromycinbenzoxaborole1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaboroleantibacterialconjugates of antibiotics |
| spellingShingle | Gennady B. Lapa Elena P. Mirchink Elena B Isakova Maria N Preobrazhenskaya Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin Journal of Enzyme Inhibition and Medicinal Chemistry Antibiotic macrolactone macrolide clarithromycin benzoxaborole 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole antibacterial conjugates of antibiotics |
| title | Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin |
| title_full | Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin |
| title_fullStr | Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin |
| title_full_unstemmed | Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin |
| title_short | Two approaches to the use of benzo[c][1,2]oxaboroles as active fragments for synthetic transformation of clarithromycin |
| title_sort | two approaches to the use of benzo c 1 2 oxaboroles as active fragments for synthetic transformation of clarithromycin |
| topic | Antibiotic macrolactone macrolide clarithromycin benzoxaborole 1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborole antibacterial conjugates of antibiotics |
| url | http://dx.doi.org/10.1080/14756366.2016.1261129 |
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