- Hybrids of macrolides and nucleobases or nucleosides
-
A few examples of hybrids/conjugates/chimeras of erythromycin A derivatives and nucleobases (uracil and thymine) or thymidine-derived nucleosides are reported. Linkers and reaction conditions have been investigated to avoid the degradation of the macrolide moiety (glycoside hydrolysis, ring cleavage, dehydration, etc.). (C) 2000 Elsevier Science Ltd.
- Costa, Anna M.,Vilarrasa, Jaume
-
-
Read Online
- Synthesis and antibacterial activity of new 9-O-arylpropenyloxime ketolides
-
A novel series of 9-O-arylpropenyloxime ketolide was synthesized and evaluated for their antibacterial activity. This series of ketolide exhibited potent activity against clinically isolated gram-positive strains including Staphylococcus pneumoniae and St
- Nam, Ghilsoo,Kim, Yang Soo,Choi, Kyung Il
-
-
Read Online
- Using chemical probes to investigate the sub-inhibitory effects of azithromycin
-
The antibacterial drug azithromycin has clinically beneficial effects at sub-inhibitory concentrations for the treatment of conditions characterized by chronic Pseudomonas aeruginosa infection, such as cystic fibrosis. These effects are, in part, the result of inhibition of bacterial biofilm formation. Herein, the efficient synthesis of azithromycin in 4 steps from erythromycin and validation of the drug's ability to inhibit biofilm formation at sub-MIC (minimum inhibitory concentration) values are reported. Furthermore, the synthesis of immobilized and biotin-tagged azithromycin analogues is described. These chemical probes were used in pull-down assays in an effort to identify azithromycin's binding partners in vivo. Results from these assays revealed, as expected, mainly ribosomal-related protein binding partners, suggesting that this is the primary target of the drug. This was further confirmed by studies using a P. aeruginosa strain containing plasmid-encoded ermC, which expresses a protein that modifies 23S rRNA and so blocks macrolide entry to the ribosome. In this strain, no biofilm inhibition was observed. This work supports the hypothesis that the sub-inhibitory effects of azithromycin are mediated through the ribosome. Moreover, the synthesis of these chemical probes, and proof of their utility, is of value in global target identification in P. aeruginosa and other species.
- Glansdorp, Freija G.,Spandl, Richard J.,Swatton, Jane E.,Loiseleur, Olivier,Welch, Martin,Spring, David R.
-
-
Read Online
- Design, synthesis and biological evaluation of a halogenated phenazine-erythromycin conjugate prodrug for antibacterial applications
-
There is a significant need for new antibacterial agents as pathogenic bacteria continue to threaten human health through the acquisition of resistance and tolerance towards existing antibiotics. Over the last several years, our group has been developing
- Yang, Hongfen,Liu, Ke,Jin, Shouguang,Huigens III, Robert W.
-
-
Read Online
- Roxithromycin intermediate preparation method
-
The invention discloses a preparation method of a roxithromycin intermediate. The method comprises the following steps: (i) mixing and reacting a compound, triethylamine and hydroxylamine hydrochloride, the structures of which are shown in a formula II, to obtain the compound the structure of which is shown in a formula III; (ii) mixing the compound the structure of which is shown in the formula III, with methanol or ethanol, alkalinizing and mixing with water, to obtain a compound the structure of which is shown in the formula I.
- -
-
Paragraph 0057-0060; 0061-0064; 0065-0068; 0069-0076
(2017/10/05)
-
- HYDROGEN BOND FORMING FLUORO KETOLIDES FOR TREATING DISEASES
-
The invention described herein pertains to a novel macrolide antibacterial agent of formula (I): A-L-Q, as defined herein, and pharmaceutically acceptable salts, solvates, and hydrates thereof. Inter alia, the new macrolide antibacterial agent is active a
- -
-
Page/Page column 31-32
(2012/03/27)
-
- Chemistry and biology of macrolide antiparasitic agents
-
Macrolide antibacterial agents inhibit parasite proliferation by targeting the apicoplast ribosome. Motivated by the long-term goal of identifying antiparasitic macrolides that lack antibacterial activity, we have systematically analyzed the structure-activity relationships among erythromycin analogues and have also investigated the mechanism of action of selected compounds. Two lead compounds, N-benzylazithromycin (11) and N-phenylpropylazithromycin (30), were identified with significantly higher antiparasitic activity and lower antibacterial activity than erythromycin or azithromycin. Molecular modeling based on the cocrystal structure of azithromycin bound to the bacterial ribosome suggested that a substituent at the N-9 position of desmethylazithromycin could improve selectivity because of species-specific interactions with the ribosomal L22 protein. Like other macrolides, these lead compounds display a strong "delayed death phenotype"; however, their early effects on T. gondii replication are more pronounced.
- Lee, Younjoo,Choi, Jun Yong,Fu, Hong,Harvey, Colin,Ravindran, Sandeep,Roush, William R.,Boothroyd, John C.,Khosla, Chaitan
-
experimental part
p. 2792 - 2804
(2011/06/24)
-
- Synthesis and antibacterial activity of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether
-
A series of new 4″-O-carbamates of 11,12-cyclic carbonate erythromycin A 6,9-imino ether were synthesized and evaluated for their in vitro antibacterial activity. All the desired compounds demonstrated favorable activity (0.03 μg ml-1) against erythromycin-susceptible Streptococcus pneumoniae comparable to the references, exhibiting 133-fold higher activity than precursor 2 or 3. Similarly, all of the analogs exhibited improved activity against the erythromycin-resistant S. pneumoniae encoded by the erm gene and the erm and mef genes, showing 4-32-fold more effectiveness than erythromycin A.
- Zhang, Ling,Jiao, Bo,Yang, Xiangrui,Liu, Lin,Ma, Shutao
-
experimental part
p. 243 - 247
(2012/02/16)
-
- Design, synthesis, and anti-Helicobacter pylori activity of erythromycin A (E)-9-oxime ether derivatives
-
The synthesis and anti-Helicobacter pylori (H. pylori) activity evaluation of a new series of erythromycin A (E)-9-oxime ether derivatives are described. These compounds exhibited comparable in vitro anti-H. pylori activity and improved acid stability com
- Nam, Ghilsoo,Kang, Tae Won,Shin, Jung Hyu,Choi, Kyung Il
-
p. 569 - 572
(2007/10/03)
-
- NOVEL MACROLIDE DERIVATIVES HAVAING EFFECT OF POTENTIATING ANTIFUNGAL ACTIVITY
-
The present invention relates to substances having enhancing effect for activities ofazole antifungal agents, acting at low concentration and within short term against fungal infection and making possibility for reducing frequency of appearance of resista
- -
-
Page/Page column 14
(2008/06/13)
-
- TRICYCLIC MACROLIDE ANTIBACTERIAL COMPOUNDS
-
Antibacterial compounds having formula (I) and formula (II), and salts, prodrugs, and salts of prodrugs thereof, processes for making the compounds and intermediates used in the processes, compositions containing the compounds, and methods for prophylaxis
- -
-
Page/Page column 61; 80
(2008/06/13)
-