Tetracycline - slideshare
chemical aspects and SAR of Tetracyclins, Macrolides and Chloramphenicol. The PPT contains contains the description of the synthesis. Chloramphenicol - authorSTREAM Presentation. isomers are virtually inactive. . 6 STRUCTURE ACTIVITY RELATIONSHIP. CHLORAMPHENICOL ppt Download as PPT, PDF, TXT or read online from Scribd. Flag for Structure Activity Relationship ▻ The aromatic ring is essential.
Hydrolysis of chloramphenicol with either acid or alkali produces dichloroacetic acid together with an optically active base C 9 H 12 O 4 N 2. SAR of p — nitro phenyl group: Replacement of the nitro group by the other substituents leads to reduction in activity. Shifting of nitro group from the para position also reduces the antibacterial activity. The p-nitro phenyl group may be replaced by other aryl structure without appreciable loss of activity.
Replacement of phenyl group by the alicyclic moieties results in less potent compounds. SAR of 1,3 — propanediol: The primary alcoholic group on C-1 atom if modified, results in a decrease in activity hence the alcoholic group seems to be essential for activity. SAR of dichloracetamido side chain: The synthesis put forward by Long et al. Chloramphenicol, a broad-spectrum antibiotic, is active not only against bacteria but also against other microorganisms, such as rickettsia. Chloramphenicol has excellent activity against anaerobes.
The drug is either bactericidal or bacteriostatic, depending on the organisms. It readily enters the normal CSF. The drug inhibits the hepatic mixed-function oxidases. Excretion of the drug depends on its conversion in the liver to a glucuronide, which is then secreted by the renal tubule.
Structure-activity relationship of...
Chloramphenicol is also secreted into breast milk. Haemolytic anemia occurs in patient with low levels of glucose 6-phosphate dehydrogenase. The effect usually occurs weeks or months after treatment has been stopped, and a genetic predisposition may be involved.
Chloramphenicol should be discontinued if the complete blood count drops below 2. Removal of 4-dimethyl amino group further decrases activity. Activity is largely retained in primary and secondary amines but decreases with higher aklyl amines.
Esters at C12a is inactive except formyl esters. Alkylation of C11a also leads t inactive compounds. Inonisable beta ketones is essential at C11 and C Substitutions at C 5, 6, 7, 8, and 9 represent largely hydrophobic northern and western faces of molecule. Electron withdrawing group at C7 like Cl, nitro or electron donatin dimethyl amino; both enhances the activity.
Chemistry And SAR of Protein Synthesis Inhibitors |authorSTREAM
Tetracyclines inhibit bacterial protein synthesis by blocking the attachment of the t-RNA-amino acid to the ribosome. Tetracyclines can also inhibit protein synthesis in the host, but are less likely to reach the concentration required because eukaryotic cells do not have a tetracycline uptake mechanism.
By Gaurav Kayal Stability under acid condition: By Gaurav Kayal Formation of 4-Epitetracycline: Under acidic conditions, a 1: By Gaurav Kayal Stability under base condition: Stability under base condition In basic medium, ring C of tetracycline is opened to form isotetracycline. By Gaurav Kayal Formation of metal chelates: Formation of metal chelates Stable chelate complexes are formed by the tetracyclines with many metals, including calcium, magnesium, and iron.
Such chelates are usually very insoluble in water. The affinity of tetracyclines for calcium causes them to incorporated into newly forming bones and teeth as tetracycline-calcium orthophosphated complexes. Deposits of these antibiotics in teeth cause a yellow discoloration. The tetracyclines are distributed into the milk of lactating mothers and will cross the placental barrier into the fetus. Chloramphenicol is an antibiotic produced by Streptomyces venezuelae and other soil bacteria that was first discovered in and is now exclusively produced synthetically.
By Gaurav Kayal Introduction D- - -threo p -nitrophenyldichloroacetamido-1,3-propanediol Stereochemistry: By Gaurav Kayal With two chiral centers it is one of four diastereomers only one of which 1R, 2R is active.
Stereochemistry A molecule, with two chiral centers, has four isomers diastereomers. A molecule, with two chiral centers, has four isomers diastereomers. By Gaurav Kayal Chemical properties: Chloramphenicol is bacteriostatic by inhibition of protein biosynthesis. Its toxicities prevent Chloramphenicol from being more widely used.
The major adverse effect of chloramphenicol is a risk of fatal irreversible aplastic anemia that occurs after therapy and does not appear to be related to dose or administration route. Reversible bone marrow suppression and several other adverse effects including gastrointestinal problems, headache, and mild depression have also been noted.
By Gaurav Kayal Para nitro phenyl can be replaced by other aryl structures without appreciable loss of activity. Substitution of phenyl ring other than nitro group or any other functinal group does not decreases the activity. But all such compounds have less activity than chloramphenicol.