Structureactivity relationships and mechanism of action. Article in japanese omura s1, morimoto s, nagate t, adachi t, kohno y. Other aerobic bacteria that clarithromycin has activity against include c. Design, synthesis and structureactivity relationship. Commercial software exists for the prediction of human toxic endpoints. Erythromycin and its analogs are used to treat respiratory tract and other. Cheminformaticsbased enumeration and analysis of large. Structureactivity relationships for three macrolide antibiotics in haemophilus influenzae. The cfu data were analyzed and plotted with sas software, version 8. Structureactivity relationships and mechanism of action of macrolides derived from erythromycin as antibacterial agents. Clarithromycin does not achieve significant levels in the cerebrospinal fluid. They are used in the treatment of a variety of infections, including communityacquired respiratory tract infections and mycobacterial infections. Additionally, when physicochemical properties or structures are expressed by numbers, one can find a mathematical relationship, or quantitative structure activity relationship, between the two. Azithromycin and clarithromycin are derivatives of the older macrolide antibiotic erythromycin.
As a macrolide antibiotic, clarithromycin is used in the treatment of infections caused by bacteria. The toxicity estimation software tool test was developed to allow users to easily estimate the toxicity of chemicals using quantitative structure activity relationships qsars methodologies. As an example, biological activity can be expressed quantitatively as the concentration of a substance required to give a certain biological response. A new crystal structure of clarithromycin springerlink.
Risk assessment and management of genotoxic impurities in. Clarithromycin is administered twice a day for most indications that require four times the equivalent dose of erythromycin. Form iii of clarithromycin, contrary to form i, is more thermodynamically stable than form ii used currently on the market. Structureactivity relationships for three macrolide. The structureactivity relationship sar indicated that the introduction of a suitable secondary amine substituent at the 9position might be beneficial for potency. School of life science, beijing institute of technology, beijing 81, china. It is categorised as a broadspectrum antibiotic which protects against mycoplasma, chlamydia and mycobacteria and other gramnegative and gram. Clarithromycin has been linked to rare instances of acute liver injury that can be severe and even fatal. Like erythromycin, clarithromycin has poor activity against gram negative bacteria. Due to which it has improved acid stability and oral absorption compared with erythromycin. Clarithromycin is a macrolide antibiotic and a cyp3a4 inhibitortarget.
Ask your health care provider about possible side effects from clarithromycin. Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria. Clarithromycin is usually bacteriostatic, but may be bactericidal depending on the organism and the drug concentration. Qsars are mathematical models used to predict measures of toxicity from the physical characteristics of the structure of chemicals known as molecular. Get emergency medical help if you have signs of an allergic reaction to clarithromycin. Simple uv spectrophotometric assay of clarithromycin. Structure activity relationship sar is an approach designed to find relationships between chemical structure or structuralrelated properties and biological activity or target property of studied compounds. This ed material has been downloaded from a licensed data provider and is not for distribution, except. Clarithromycin is the 6omethyl ether of erythromycin a, clarithromycin is a macrolide antibiotic used in the. Clarithromycin prevents smokeinduced emphysema in mice. Be careful when using any machinery, driving a vehicle, or doing any other activity that needs you to be fully alert. This paper describes the synthesis, structureactivity relationships, antibacterial activities, metabolism and clinical efficacies of cam, a new macrolide antibiotic.
Clarithromycin belongs to a group of drugs called macrolide antibiotics which work by inhibiting protein synthesis, stopping bacterial growth and reproduction. A recent study showed that a new derivative of erythromycin without antibiotic activity, em703, demonstrated antiinflammatory and antifibrotic activities in a bleomycininduced lung injury model, suggesting that the structureactivity relationship of macrolides may differ in their antibiotic and antiinflammatory activities against emphysema. Clarithromycin differs from erythromycin only by methylation of the hydroxyl group at the 6 position. A prior study examining differences in the activities of erythromycin and azithromycin on cellular functions in the gramnegative pathogen, haemophilus influenzae. Tested against contemporary clinical bacteria from a global surveillance program. Reaction of the 3bromomethylindazole 4 6 with an excess or equivalent amount of the appropriate amine 12a or 12b, etc. Additionally, clarithromycin has only a low incidence of the gi side effects associated with the use of erythromycin. Simple uv spectrophotometric assay of clarithromycin dr. Nature nurtures the design of new semisynthetic macrolide antibiotics.
Taking palmatine pmt as the lead, 20 new pmt derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole mtzresistant helicobacter pylori h. The clinical use of clarithromycin in treating tuberculosis is limited to. A dose of 2 g twice a day for up to 24 weeks results in a halflife 18 h, and has been safe in. Find patient medical information for clarithromycin oral on webmd including its uses, side effects and safety, interactions, pictures, warnings and user ratings. Unfortunately, clarithromycin can cause drug interactions because of its ability to inhibit the cytochrome p450 cyp 3a4 enzyme. Ask your health care provider if there are interactions between clarithromycin and the other medicines you take. Cyp3a4clarithromycin is a macrolide antibiotic used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia especially atypical pneumonias associated with chlamydophila pneumoniae, skin. I am not sure why were you prescribed clarithromycin. Toxicity estimation software tool test safer chemicals. Clarithromycin is used for treating a number of common bacterial infections in both children and adults. We built a structureactivity relationship sar model for evaluating hepatotoxicity. For this purpose, two different software products were applied in this study to calculate ecotoxicity. Maximum tolerated dose of clarithromycin is 3 g twice a day.
Clarithromycin is an acidstable orally administered macrolide antimicrobial drug, structurally related to erythromycin. Development of novel erythromycin derivatives with. Cyp 3a4 plays a role in the metabolism of colchicine and pgp is responsible for the efflux of colchicine across membranes. Structure activity relationship study sar the cresset software forge is a molecular design and sar structure activity relationship interpretation tool that generates and uses molecular alignments as a way to make meaningful comparisons across chemical series. The consumption of alcohol with clarithromycin can worsen the sleepiness. Safila naveed1and fatima qamar1 1faculty of pharmacy jinnah university for women karachi email. Clarithromycin is often used for pneumonia, bronchitis, and. The results of quantitative structureactivity relationship qsar analyses on three series of cyp3a4 inhibitors are reported for enzyme inhibition expressed as ki values. Selected from data included with permission and ed by first databank, inc. In vitro and in vivo activities of macrolide derivatives against. Clarithromycin is a potent inhibitor of the activity of cytochrome p450 cyp 3a4 and pglycoprotein pgp. Antibiotic drugs, information, description on clarithromycin.
Clarithromycin is a white to offwhite crystalline powder. Inclusion or absence of a drug label on the aidsinfo site does not imply endorsement or lack thereof by aidsinfo. Clarithromycin can be taken by mouth as a pill or liquid. Highdose clarithromycin is an active monotherapy for. Pdf structureactivity relationships of ketolides vs. The choice of the dose of clarithromycin used in this trial is based on safety and pharmacokinetic data. As such it is the concept of linking chemical structure to a chemical property e. Opportunity according to chinese business association reported that in 2007, with erythromycinbased macrolide antibiotics, total global sales of more than 90 million sales of clarithromycin in the global market has risen to 15 billion u. Protein binding of clarithromycin ranges from 40 to 70% and is concentrationdependent. Clarithromycin and angioedema introduction clarithromycin is a bacteriostatic antibiotic belonging to group of macrolides. This prescription medication is also used to treat and prevent a serious infection that can occur in people with aids. As part of the research program aimed at discovering next. Synthesis and structureactivity relationship of palmatine. Pdf from erythromycin to azithromycin and new potential.
Structureactivity relationships, some of which are unique to m. Clarithromycin is the generic form of the brandname prescription drug biaxin, an antibiotic used to treat bacterial infections. Clarithromycin is a semisynthetic macrolide antibiotic used for a wide variety of mildtomoderate bacterial infections. By employing computeraided tools and heuristics, such as 3dmolecular docking andor quantitative structureactivity relationship qsar models 21, 22, one could predict the potential activity and synthetic feasibility of compounds in order to prioritize analogues with desirable structural and molecular properties. Structureactivity relationships for three macrolide antibiotics in.
Significantly, clarithromycin demonstrates greater in vitro activity than. The molecular formula is c38h69no, and the molecular weight is 747. Trainable structureactivity relationship model for. A new crystal structure of clarithromycin jianhua liang, guowei yao a crystal structure of clarithromycin single acetonitrile solvate. Synthesis of erythromycin derivatives and structureactivity relationships. Predicting clinical effects of cyp3a4 modulators on. Clarithromycin is a semisynthetic macrolide antibiotic. Clarithromycin side effects, uses, dosage, overdose.
Clarithromycin biaxin is a well known macrolide antibiotic used in the management of helicobacter pylori, uncomplicated skin, and upper and lower respiratory tract infections. Some of these infections include strep throat, sinus infections, and pneumonia. Odesosaminyl clarithromycin derivatives were designed and synthesized. Structural basis for the interaction of antibiotics with. Quantitative structureactivity relationships qsars in. Several fdaapproved drug labels may be available for clarithromycin. The infections may include pneumonia, respiratory tract infections, lyme disease, strep throat, skin infections, h. Clarithromycin may cause rarely seizures in some people.
Clarithromycin is an antibiotic medication commonly prescribed to treat strep throat, sinus infections, bronchitis, pneumonia, skin infections, ear infections, as well as other bacterial infections. Clarithromycin is used orally for the treatment of pharyngitis and tonsillitis, mild to moderate respiratory tract infections acute bacterial exacerbation of chronic bronchitis, acute maxillary sinusitis, communityacquired pneumonia, uncomplicated skin and skin structure infections, and acute otitis media caused by susceptible organisms. Aidsinfo provides the following drug label solely as an example of the labels available for clarithromycin. The identity of the two major clar metabolites present in microsome incubates, 14rhydroxyclar andndesmethylclar, was confirmed by ms. Clarithromycin drug information, uses, side effects. Clarithromycin, sold under the brand name biaxin among others, is an antibiotic used to treat various bacterial infections. The 6omethyl ether of erythromycin a, clarithromycin is a macrolide antibiotic used in the treatment of respiratorytract, skin and softtissue infections. The elimination halflives of clarithromycin and 14hydroxyclarithromycin are approximately 3 to 7 and 5 to 9 hours respectively. The six compounds 6, 8, 10a,b and 11a,b were prepared as the first set of analogues. It prevents bacteria from growing by interfering with their protein synthesis.
Clarithromycin was granted marketing authorization in 1990. Clarithromycin has an invitro activity that is similar or greater than that of erythromycin against erythromycinsusceptible organisms. In vitro studies were conducted to identify the hepatic cytochrome p450 cyp proteins involved in the oxidative metabolism of 14 cclarithromycin clar in the presence of native human liver microsomes. Quillen college of medicine, east tennessee state university, johnson city, tn 37614, usa. Clarithromycin 500mg tablets summary of product characteristics smpc by accord healthcare limited. A new structureactivity relationship sar model for. It has a broad spectrum of antimicrobial activity, similar to that of erythromycin and inhibits a range of grampositive and gramnegative organisms, atypical pathogens and some anaerobes. Learn about drug interactions between clarithromycin oral and fluoxetine oral and use the rxlist drug interaction checker to check drug combinations. Oxidative metabolism of clarithromycin in the presence of. There is a relationship between molecular structures and their biological activity, and this principle is referred to as structure activity relationship sar. Clarithromycin tablet may also be used along with other medicines in the treatment of certain conditions as recommended by the doctor. How long does it take for the clarithromycin to work. Quantitative structureactivity relationship wikipedia.
Taken into account by the software are key information such as positions. The efficient synthesis routes of 6deoxydesosamine donors 8 and 11 were developed and the methodology of glycosylation of clarithromycin 4. In our continuing structureactivity relationship study of a new class of erythromycin a ema derivatives with antiproliferative activity, a new series of denmethyl ema dimers jointed by a fouratom linker, ch2ch chch2, were prepared and their antiproliferative activity against three human tumor cell lines was evaluated by mtt assay. Learn about drug interactions between clarithromycin oral and prednisone oral and use the rxlist drug interaction checker to check drug combinations. This includes strep throat, pneumonia, skin infections, h. The concentration of erythromycin was 71149 ng l1 in river water in.
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