4 5. Figure 14.9 There are several classes of antibacterial compounds that are typically classified based on their bacterial target. How Are Antibiotics Classified? (Functions & Side Effects ... Topoisomerase II : to convert the +ve supercoiling to -ve supercoiling. Connecting the methoxy or hydroxy group at carbon-8 atom to a dimethylamino group at nitrogen-1 atom (compound B) displayed superior in vitroand in vivoantibacterial activity as compared to ofloxacin and ciprofloxacin in . The limit of detection and the limit of quantification for . Levofloxacin Anhydrous is the anhydrous form of levofloxacin, a broad-spectrum, third-generation fluoroquinolone antibiotic and optically active L-isomer of ofloxacin with antibacterial activity. 16. Ciprofloxacin a. Three antibiotic sensitivity disks appear on this medium: penicillin, sulfa, and ciprofloxacin (clockwise from top). Side effects are rarely seen when taking this drug. a. Quinolones Antimicrobials such as nalidixic acid, ciprofloxacin, ofloxacin, pefloxacin etc bind to the A subunit of DNA gyrase (topoisomerase) and prevent supercoiling of DNA, thereby inhibiting Classification of antibiotics. Cycloserine is an antimetabolite of D-Alanine, a . Metronidazole is one of the mainstay drugs for the treatment of anaerobic bacterial infections, protozoal infections, and microaerophilic bacterial infections. Antibiotics are effective against either a small group of bacteria (narrow-spectrum) or a wide range . PREPARATION AND CHARACTERIZATION OF CIPROFLOXACIN LOADED TRANSDERMAL PATCHES Abstract. Possible serious side effects are central nervous system effects, hyperglycemia, and C. difficile associated diarrhea. Sulpha is an alternate spelling of the common name for sulfa drugs or sulfonamide antibiotics. The larger the zone of bacterial inhibition, the more effective the antibiotic is against the bacteria. 17. 1) is a newly synthesized fluoroquinolone antibacterial agent that has been demonstrated to have broad antibacterial spectrum, good bioavailability, prolonged serum half-life, improved safety and tolerability, as well as favorable pharmacokinetic parameters [ 7 - 9 ]. Development of antimicrobials for clinical use has been most successful in targeting essential components of 5 general areas of bacterial metabolism: cell wall synthesis, protein synthesis, RNA synthesis, DNA synthesis, and intermediary metabolism ().It is beyond the scope of this discussion to cover each of these areas in detail. How do Antibiotics Work? Administration Ciprofloxacin is available both orally and intravenously. Antimicrobials—In the case of infectious diseases, this means that the medication is not an antibiotic in the strict sense of originating from a germ or virus, but it is often used in the treatment of pathogens.. Bactericidal—Antimicrobial action that kills bacteria as well as inhibits their development.. Bacteriostatic—Antimicrobial activity inhibits cell development but does not kill them. Trimethoprim is a synthetic derivative of trimethoxybenzyl-pyrimidine with antibacterial and antiprotozoal properties. As a pyrimidine inhibitor of bacterial dihydrofolate reductase, trimethoprim binds tightly to the bacterial enzyme, blocking the production of tetrahydrofolic acid from dihydrofolic acid.The antibacterial activity of this agent is potentiated by sulfonamides. In the current study, synthesis, characterization, and biological evaluation of some more lipid based prodrugs/compounds of ciprofloxacin and norfloxacin has been carried out. Can be due to an efflux pump b. CIPROFLOXACIN SYNTHESIS (CONT..) 16. Ciprofloxacin is also effective for bacterial prostatitis, noncomplicated gonorrhea, osteomyelitis, and pulmonary infections. Some antibacterial drugs work by inhibiting nucleic acid synthesis (Table 10.5). No matter how active or potentially active a new molecular entity (NME) Levofloxacin, sparfloxacin are used for treatment of upper and lower respiratory tract infections. Ciprofloxacin is one of the few oral antibiotics able to treat P. aeruginosa infections. Chloramphenicol is an organochlorine compound that is dichloro-substituted acetamide containing a nitrobenzene ring, an amide bond and two alcohol functions. Mechanism of action of lomefloxacin. The aim of this research was to formulate a matrix-type transdermal therapeutic system containing drug ciprofloxacin with different ratios of hydrophobic (ethyl cellulose) polymer by solvent evaporation technique, using 15% w/w of dibutyl phthalate to the polymer weight, incorporated as plasticizer. They transfer a lot of resistance genes from one bacterium to another. Antimicrob Agents Chemother. 14. Piddock LJ(1), Hall MC, Wise R. Author information: (1)Department of Medical Microbiology, University of Birmingham Medical School, United Kingdom. The β-lactams inhibit cell wall synthesis and thereby increase the permeability of the bacterium to the aminoglycosides. DNA gyrase is a type II topoisomerase that introduces or removes negative supercoils, forms or resolves catenanes, and knots or unknots DNA (Gellert et al., 1976; Kreuzer and Cozzarelli, 1980; Liu et al., 1980 ). Antibiotics: Antibiotics are the chemical therapeutic agents of microbial or synthetic or semi-synthetic origin which in lower concentration inhibit the growth of other microorganisms. Quinolones are a key group of antibiotics that interfere with DNA synthesis by inhibiting topoisomerase, most frequently topoisomerase II (DNA gyrase), an enzyme involved in DNA replication. Contribute to nearai/program_synthesis development by creating an account on GitHub. The 1st generation of the quinolones begins with Nalidixic acid in 1962 for the treatment of Urinary Tract Infections in humans. 1 It reportedly carries 8 to 128-fold more activity against both gram-negative and gram-positive bacteria compared to R-(+)-ofloxacin 1 and remains stereochemically stable following administration (i.e. 20. Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities. However, antibiotic resistance genes are not confined to the clinic; instead they are widely prevalent in different bacterial populations in the environment. Ciprofloxacin complex exerts its disinfectant effect by inhibiting the synthesis of DNA in bacteria, preventing their growth and the spread of infection. Levofloxacin = higher urine levels Levofloxacin demonstrated rapid bactericidal activity against E coli in the urine (with MICs ≤32 µg/mL at 1.5 hr). Normal volunteers showed heart/lung and heart/blood activity ratios . B] On the basis of origin. 11 Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action . Of these, antibacterial agents are by far the most commonly used and thus are the focus of this article, although similar principles apply to the other agents as well. Streptomycin is a amino cyclitol glycoside that consists of streptidine having a disaccharyl moiety attached at the 4-position. Therefore, to understand development of antibiotic resistance in pathogens, we need to consider important reservoirs of resistance . The founding member of the quinolone drug class, nalidixic acid, is a naphthyridine that was first isolated by George Lesher and colleagues in 1962 as a byproduct of chloroquine synthesis (Figure (Figure1 1). Inhibition of cell wall synthesis 2). Drug detection is crucial for monitoring the concentration of specific drugs in the human body or veterinary animals or the environment. Synthesis 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1H-quinoline- 3-carboxylic acid 33 34. The terms antimicrobial, antibiotic, and anti-infective encompass a wide variety of pharmaceutical agents that include antibacterial, antifungal, antiviral, and antiparasitic drugs. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the . the one-step synthesis presented in The fused hybrids 3a and 3b were prepared in the one-step synthesis presented in Scheme Scheme 1.1.Compounds Compounds 1a1a andand [21][21] 1b1b were were coupled coupled to ciprofloxacin to ciprofloxacin H (2) using the reagents 1- N(2) using O the Oreagents ethyl-3-(3-dimethylaminopropyl)carbodiimide H 1 . " ANTIBIOTICS THAT INTERFERE WITH THE METABOLIC SYSTEMS FOUND IN MICRO-ORGANISMS AND NOT IN MAMALIAN CELLS ARE THE MOST SUCCESSFUL ANTI-INFECTIVE AGENTS" For example, • Antibiotics that interfere with the synthesis of bacterial cell walls have a high potential for selective toxicity. This product is not recommended for use once a day. Ciprofloxacin is administered orally twice daily for 7 to 14 days or at least two days after signs and symptoms of the infection are over. The method was linear between 0.3 μg/g and 15 μg/g for levofloxacin and ciprofloxacin with coefficient of correlation (r) ≥0.999. Neomycin. A diagnosis of kidney infection (pyelonephritis) is made, and the decision is made to use a beta-lactam antibiotic that has both an appropriate antibacterial spectrum of activity, and good . Streptomycin. An improved process for the synthesis of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid (Ciprofloxacin) or and its acid addition salts preferablyhydrochloride salt with high yield and high purity, the process comprising of reacting 6-fluoro-7-chloro-1-cyclopropyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid with piperazine in presence of a catalyst in . Emergence of antibiotic resistant pathogenic bacteria poses a serious public health challenge worldwide. Rarely, a secondary intracranial hypertension will form accompanied by vision problems and a severe headache. It has a role as an antiinfective agent, a topoisomerase IV inhibitor, an antibacterial drug, an EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor, a DNA synthesis inhibitor, an antimicrobial agent, an . Cell walls without intact peptidoglycan cross-links are structurally weak, prone to collapse and disintegrate when the bacteria attempts to divide. Daunorubicin is an anthracycline antineoplastic antibiotic with therapeutic effects similar to those of doxorubicin.Daunorubicin exhibits cytotoxic activity through topoisomerase-mediated interaction with DNA, thereby inhibiting DNA replication and repair and RNA and protein synthesis. By selling an article at 3/4th of the marked price, there is a gain of Is most commonly due to modification of the target PBPs c. There are 4 species of Shigella: S. dysenteriae, S. flexneri, S. boydii, and S. sonnei (also referred to as group A, B, C, and D, respectively). D. Inhibition of nucleic acid synthesis These antimicrobials exploit the differences in RNA/DNA synthesis mechanism to exert selective toxicity. Sequential offline acidifications and filtrations afforded ciprofloxacin and ciprofloxacin hydrochloride. 4,5 The more commonly used fluoroquinolones ciprofloxacin and levofloxacin were approved for use in children solely . 16 Nalidixic acid was introduced into the clinic in the 1960s for the treatment of uncomplicated urinary tract infections caused by enteric bacteria. Fig 3 Antibiotics that act at the level of protein synthesis initiation. Sailaja et al. lysergic acid 8. The synthesized prodrugs/compounds have been screened for anthelmintic activity using Indian earthworms and cytotoxic activity against human lung cancer cell lines A-549 . Mechanism Explained ! Impurities can have unwanted pharmacological or toxicological effects that seriously impact product quality and patient safety. The RNA polymerase enzymes in bacteria are structurally different from those in eukaryotes . Fluoroquinolones Ciprofloxacin (Cipro), Garenoxacin MOA: Inhibition of DNA gyrase Antimicrobial spectrum: Gram-negative and Gram-positive ( Anaerobes,, S.pneumoniae and Pseudomonas) Dose: 250-500 mg qid x 7-10 days Contraindications: <18 yrs old, pregnancy Adverse events: spontaneous tendon rupture Drug interactions: probenecid, warfarin . Drug interactions with fluoroquinolones 29. The aim of this research was to formulate a matrix-type transdermal therapeutic system containing drug ciprofloxacin with different ratios of hydrophobic (ethyl cellulose) polymer by solvent evaporation technique, using 15% w/w of dibutyl phthalate to the polymer weight, incorporated as plasticizer. It is effective in treating acute infectious diarrhea, including traveler's diarrhea and enteritis. The first fluoroquinolone, nalidixic acid, was introduced in 1964 and for the last two decades has been approved for the treatment of urinary tract infections (UTIs) in children aged 3 months and older; however, it is rarely used. Herein, we report the synthesis of novel hybrid molecules comprised of two different hindered nitroxides linked to the piperazinyl secondary amine of ciprofloxacin via a tertiary amine . But no matter what class or kind of antibiotics exists or is discovered, all of them operate by one of the following mechanisms: 1). [6,7] Macrolides These affect the early stage of protein synthesis, namely translocation, by targeting the conserved sequences of the peptidyl transferase center of the 23S r-RNA of the 50S ribosomal subunit. DNA gyrase relaxes supercoiled DNA molecules and initiates transient breakages and rejoins . Adverse effects of Quinolones a. 18. cyclopropyl group of ciprofloxacin by an oxetane (compound A) had increased Gram positive activity relative to ciprofloxacin. Antibiotics can have bacteriostatic (i.e., stopping bacterial reproduction), bactericidal (i.e., killing bacteria), or both mechanisms of action. Take . ORGANIC SYNTHESIS. The parent of the streptomycin class It has a role as an antimicrobial agent, an antimicrobial drug, an antibacterial drug, a protein synthesis inhibitor, a bacterial metabolite and an antifungal agrochemical. Pregnancy. Tablets have been marketed since 1987 for the treatment of a wide variety of infectious diseases in adults [1]. Measurement Science and Technology.2007;18(3). PREPARATION AND CHARACTERIZATION OF CIPROFLOXACIN LOADED TRANSDERMAL PATCHES Abstract. " ANTIBIOTICS THAT INTERFERE WITH THE METABOLIC SYSTEMS FOUND IN MICRO-ORGANISMS AND NOT IN MAMALIAN CELLS ARE THE MOST SUCCESSFUL ANTI-INFECTIVE AGENTS" For example, • Antibiotics that interfere with the synthesis of bacterial cell walls have a high potential for selective toxicity. action of ciprofloxacin results from the inhibition of topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repa ir, and recombination. Corticosteroids may play an important role in TB infection by promoting reactivation of latent infection. Ofloxacin • Ofloxacin is a racemic mixture, which consists of 50% levofloxacin (the biologically active component) and 50% of its "mirror image" or enantiomer dextrofloxacin. Inhibition of protein synthesis 3). DNA gyrase has the ability to introduce a double-stranded break in DNA and it is thought to have an important role in these . Ciprofloxacin (Cipro, Cipro XR, Proquin XR) is an antibiotic drug prescribed to treat a variety of bacterial infections (sinus, tooth, UTI, gonorrhea, prostatitis). This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Medicinal chemists are extensively involved in. About Synthesis Slideshare Ephedrine . Lab tests indicate the presence of white blood cells and E.coli in her urine. Latter compound is reacted with iso-propylamine to give propranolol. Dear Reader, do you have any idea that, "How do antibiotics work" .You might be having a fair idea about it, but the same thing has been brought out in detail in this article below with Mode of action of antibiotics & Mechanism Of Action Of Antibiotics. As bacterial biofilms are often refractory to conventional antimicrobials, the need for alternative and/or novel strategies for the treatment of biofilm related infections has become of paramount importance. Ciprofloxacin hydrochloride has IUPAC Shigellosis is an acute infection of the intestine caused by bacteria in the genus Shigella. The drug rifampin is a semisynthetic member of the rifamycin family and functions by blocking RNA polymerase activity in bacteria. Out of the research around 40% of lipophilic drug candidates fail to reach the market although exhibiting potential pharmacodynamic activities [6]. 1. These topoisomerase inhibitors are widely used for the treatment of urinary tract and other infections. Some antibiotics are also used against parasitic infections. The products of Qnr plasmid block the function of ciprofloxacin on purified DNA gyrase and topoisomerase IV. Special Offer to SlideShare Readers . Levofloxacin is a fluoroquinolone antibiotic and the optical S-(-) isomer of racemic ofloxacin. It has a role as an antimicrobial agent, an antibacterial drug, a protein synthesis inhibitor, an Escherichia coli metabolite, a Mycoplasma genitalium metabolite and a geroprotector. 19. Corticosteroids may modify symptoms of some forms of extrapulmonary TB, although randomized, placebo-controlled studies are needed before corticosteroids will have a definitive place in the stan … A] On the basis of chemical structure. Synthesis and characterization of Salicylic. Resistance to B lactams a. SYNTHESIS OF CIPROFLOXACIN USE RETROSYNTHESIS TECHNIQUE IT WOULD MAKE YOUR LIFE EASY.. ! No separation of intermediates was required throughout the synthesis when a single acylation reaction was applied to remove the main byproduct, dimethylamine. SYNTHESIS OF CIPROFLOXACIN 15. Quinolones. 1 By the 1970s, several . There by allowing the process of replication or the allows the action of DNA helicase to proceed. [ 6 , 9 ] This results in a . No separation of intermediates was required throughout the synthesis when a single acylation reaction was applied to remove the main byproduct, dimethylamine. Mode of Action. Ciprofloxacin (Fig. Pharmacodynamics. Aminoglycosides inhibit bacterial protein synthesis. Some antibacterial, antiviral and many chemotherapeutic drugs inhibit REPLICATION. Dihydropteroate synthetase activity is vital in the synthesis of folate, and folate . Ciprofloxacin Antibiotic 1. . Inhibition of membrane function 4). i. Antibiotics are a class of drugs employed mainly against bacterial infections. Clinical uses of Quinolones Ofloxacin is effective for chlamydial urethritis or cervicitis. The overall yield of the eight-step sequence was 60 %. Each class of antibacterial drugs has a unique mode of action (the way in which a drug affects microbes at the cellular level), and these are summarized in Figure 14.9 and Table 14.1. Penicillins, and other beta-lactam antibiotics, work by interfering with interpeptide linking of peptidoglycan, the a strong, structural molecule found specifically bacterial cell walls. With over 2300 references, mainly patent, for the methods of synthesis for over 700 drugs, along with the most widespread synonyms for these drugs, this book fills the gap that exists in the literature of drug . Cephalosporins, Fluoroquinolones (Ciprofloxacin), Glycopeptides (Vancomycin), Monobactams, Carbapenems. Is a defluorinated analogue of nalidixic acid b. Inhibits tropoisomerases 2 and 3 c. Has no gram positive cover d. Has a bioavailability of 30% e. May cause an arthropathy 3. Nalidixic acid was discovered by George Lesher and co-workers in a distillate during an attempt at chloroquine synthesis. Many antibacterial drugs like Novobiocin, Nalidixic acid & Ciprofloxacin inhibit the prokaryotic topoisomerase (DNA gyrase). Method of synthesis. Classification of antibiotics. Structure elucidation of pharmaceutical impurities is an important part of the drug product development process. Cipro is not safe to take if you pregnant or breastfeeding. There is not much data available about the effect of ciprofloxacin in pregnancy. The control of pharmaceutical impurities is currently a critical issue to the pharmaceutical industry. Sulfanomides Mode of Action. Take this medication by mouth usually 2 or 3 times a day, or as directed by your doctor. Jian B, Chun S, Fen L, Xin Y and Ming X, Rapid determination of Ciprofloxacin lactate in drugs by the Rayleigh light scattering technique. Int J Pharm Pharm Sci, Vol 3, Suppl 2, 2011, 45­50 47 Applications of chitosan nanoparticles Parenteral administration:‐ Following intravenous injection, many nanoparticle systems including chitosan NP exhibited a marked Note the "zone of inhibition" around each antibiotic disk. Common side effects are headache, rash, and diarrhea. Several distinct serotypes are recognized within the first 3 species. Levofloxacin diffuses through the bacterial cell wall and acts by inhibiting DNA gyrase (bacterial topoisomerase II), an enzyme required for DNA replication, RNA transcription, and repair of bacterial . Inhibitors of Nucleic Acid Synthesis. Propranolol is used for treatment of: Tremors; Angina; Hypertension; Heart rhythm disorders; Treatment and prevention of heart attacks Sailaja et al. C] On the basis of range of activity ( spectrum of activity) Chinese Journal of Pharmaceuticals, 2000, 31 [3] Zhang Ying, Xu Ji-yang. Results: Ciprofloxacin was observed to display the highest zone of inhibition (ZOI) of 17.00±1.00 mm for P. aeruginosa isolate 1 and likewise the highest ZOI of 24.50±1.50 mm for P. aeruginosa . it does not invert to the . [3] Therapeutic Uses. Summary. The overall yield of the eight-step sequence was 60 %. Tetracyclines can also cause skin photosensitivity and sensitivity to sunlight. Inhibition of Nucleic Acid Synthesis by Antibiotics. This activity will highlight the mechanism of action, adverse event profile, and other key factors pertinent to members of the interprofessional team in the care of patients being . . Ciprofloxacin is a broad spectrum antibiotic which plays an important role in inhibiting the growth of both gram-positive and gram-negative bacteria. Int J Pharm Pharm Sci, Vol 3, Suppl 2, 2011, 45­50 47 Applications of chitosan nanoparticles Parenteral administration:‐ Following intravenous injection, many nanoparticle systems including chitosan NP exhibited a marked Ciprofloxacin is a second-line agent for legionellosis. Ciprofloxacin, like other quinolones, causes arthropathy and histological changes in large joints which bear the weight of juvenile animals resulting in lameness. The inhibition of supercoiling activity of reconstituted Escherichia coli DNA gyrase by lomefloxacin, ciprofloxacin, and norfloxacin was determined. You may take it with food if stomach upset occurs. 28. Common side effects include cramps, diarrhea, sore tongue or mouth. It is cytotoxic to facultative anaerobic microorganism. Sulfonam ides and trimethoprim (TMP) block the pathway for folic acid synthesis, which ultimately inhibits DNA . ii. Antibacterial sulfonamides target a bacterial metabolic pathway as competitive inhibitors of the enzyme dihydropteroate synthetase, DHPS. directly from synthesis have a solubility below 0.1 mg/ml. Susan H arrives at the emergency department with complaints of high fever, malaise, painful urination and severe flank pain. 2. Cycloserine is an antimetabolite of D-Alanine, a . Hence, it inhibits the protein synthesis by preventing binding of t-RNA to the A site of the ribosome. 1990 Jun;34(6):1088-93. Lesser resistance with just 5 days of therapy. DR ANTHONY MELVIN CRASTO, Worlddrugtracker, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his PhD from ICT ,1991, Mumbai, India, in Organic chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with GLENMARK- GENERICS LTD, Research centre as Principal Scientist, Process . Reaction of 1-naphthol with epichlorohydrin gives 1-chloro-3-(1-naphthyloxy)-2-propanol. Synthesis of Essential Drugs describes methods of synthesis, activity and implementation of diversity of all drug types and classes. Sequential offline acidifications and filtrations afforded ciprofloxacin and ciprofloxacin hydrochloride. Inhibitors of bacterial DNA synthesis- quinolones Inhibits cytochrome P450 (CYP₁A₂) Unfortunately, bacterial resistance to quinolones is increasing world-wide, & appropriate use is needed to extend their clinical use. It is a Category C drug. 16 Metronidazole is an effective treatment for some anaerobic bacterial infections. a) Ciprofloxacin: inhibition of DNA gyrase b) Polymyxin B: inhibition of 50s protein synthesis c) Erythromycin: inhibition of 50s protein synthesis d) Sulphonamide: inhibition of folic acid 6) Cotrimoxazole is a combination of drugs a) Sulphonamide + Chloramphenicol b) Sulphonamide + Lincomycin c) Sulphonamide + Trimethoprim Fig 4 Antibiotics that act at the level of the elongation phase of protein synthesis. Generic Name Levofloxacin DrugBank Accession Number DB01137 Background. Transposons are small DNA sequences that can be transferred from one part of the chromosome to another. In this study, the phyllosilicate Effenbergerite (BaCuSi 4 O 10) was prepared by solid-state synthesis for electrochemical sensing of ciprofloxacin (CFX), one of the commonly used antibacterial drugs.Effenbergerite is naturally occurring and widely available . Marcin S.Synthesis and characterization of polyester conjugates of Ciprofloxacin.European Journal of Medicinal Chemistry.2010; 45(9): P 3844-3849. Ciprofloxacin is a quinolone that is quinolin-4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at positions 1, 3, 6 and 7, respectively. Indian earthworms and cytotoxic activity against human lung cancer cell lines A-549 to take if you or. Uncomplicated urinary tract infections caused by enteric bacteria by creating an account GitHub! 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