Pharmacognosy Antibiotics PDF

pharmacognosy Antibiotics vs Antibiotics contents : Overview 3 History of Antimicrobial Therapy 4 Sources of Antibiotics 6 Non-microbial sources of antibacterials 10 Screening for Antibiotics 17 Commercial production 25 Mechanisms of action 29 Mode of Resistance 34 Classification of antibiotics acco...

pharmacognosy Antibiotics vs Antibiotics contents : Overview 3 History of Antimicrobial Therapy 4 Sources of Antibiotics 6 Non-microbial sources of antibacterials 10 Screening for Antibiotics 17 Commercial production 25 Mechanisms of action 29 Mode of Resistance 34 Classification of antibiotics according to the biosynthetic pathways 35 Antibiotics Overview : Substances produced by various species of microorganisms: bacteria, fungi, actinomycetes to suppress the growth of other microorganisms and to destroy them. Today the term antibiotics extends to include synthetic antibacterial agents: sulfonamides and quinolones. Bactericidal: kill bacteria. Bacteriostatic: inhibit growth of susceptible bacteria, rather than killing them immediately; will eventually lead to bacterial death. Antibiotics History of Antimicrobial Therapy: 1909 Paul Ehrlich Differential staining of tissue, bacteria.Search for magic bullet that would attack bacterial structures, not ours. Developed salvarsan, used against syphilis Antibiotics 1929 Penicillin discovered by Alexander Fleming 1935 Sulfa drugs discovered 1944 Streptomycin discovered by Waksman from Streptomyces griseus Antibiotics Sources of Antibiotics: Of the antibiotics in clinical use, most are of bacterial or fungal origin. Among the bacteria, the genus Streptomyces is particularly noteworthy, as it produces antibiotics such as streptomycin, chloramphenicol, chlortetracycline, tetracycline, erythromycin and neomycin. Antibiotics The penicillins, griseofulvin (an antifungal agent) and cephalosporins are of fungal origin. The cephalosporins (cefalosporins) are broadspectrum antibiotics related both structurally and clinically to the penicillins. Being stable in acid solutions, some can be administered orally. Antibiotics Antibiotics Antibiotics Non-microbial sources of antibacterials: 1. Lichens: Many of these appear to owe their bacteriostatic and antifungal properties to usnic acid or vulpinic acid. 2. Order Coniferae: Various essential oils from Juniperus and Pinus spp. have antibacterial activity. 3. Monocotyledons: Fresh garlic owes its antibiotic action to alliine, a sulfur-containing amino acid; ginger has antibacterial properties and aloe vera gel. Antibiotics Usnic acid is naturally occurring dibenzofuran derivative found in several lichen species with the formula C18H16O7. It was the first isolated by german scientist W.Knop in 1844 and first synthesized between 1933 and 1937 by Curd and Robertson. Usnic acid was identified in many genera of lichens including Usnea , Cladonia , Hypotrachyna , Lecanora , Ramalina , Evernia ,Parmelia And Alectoria. Although it is generally believed that usnic acid is exclusively restricted to lichens in few unconfirmed isolated cases that compound was found in kombucha tea and non – lichenized ascomycetes. Antibiotics Antibiotics 4. Dicotyledons: Examples from this group are: A. -the sesquiterpene ketones of hops (humulene and lupulene) and those of myrrh; B. various sulfur containing compounds found in the Cruciferae; C. compounds found in compositous plants such as burdock, thistle, and Hieracium pilosella. The last plant has been used clinically for the treatment of Malta fever. Antibiotics D. Mastic gum is effective in the treatment of gastric ulcers and is active in low doses against Helicobacter pylori, an organism associated with this Condition. E. Cinnamon extracts have been shown to inhibit the growth and urease activity of the same organism. Antibiotics Antibiotics 5. Marine organisms. Cephalosporium acremonium. The marine streptomycete, produces istamycin A and B, active against Gram-negative and Gram-positive bacteria. 6. Plants/insects. Propolis (bee glue) prepared by bees from the pollen of various species of tree has bacteriostatic activity. Screening for Antibiotics Antibiotics Screening for Antibiotics : In searching for new antibiotics, simple and rapid methods have been developed for screening microorganisms for antibiotic –producing ability. Soil samples are rich sources of antibiotics-producing organisms. Most of these organisms are members of a group of branching procaryotic microorganisms which are given the common name actinomycetes. Antibiotics A general method for screening involves : 1. treating the soil sample with chemical that inhibit the growth of interfering bacteria and fungi but do not affect actinomycetes. E.g. - Cycloheximide as antifungal - 1:40 dilution of phenol as antibacterial agent. 2. varying dilution of the treated soil sample are streaked on agar plates containing medium that supports the growth of actinomycetes. 3. Incubation for 3-7 days at 25-30C. Then the plates are examined for characteristic colonies of actinomycetes then transferred on to fresh medium contain pathogenic M.O. Antibiotics 4. For indication of the potential usefulness of the A.B.example: activity against gram +ve bacteria (Staphylococcus aureus, Bacillus subtilis), gram-ve bacteria (E.Coli, Salmonella typhi),and antifungal (Neurospora crassa). Antibiotics 5. Bio autography assay: It is a rapid method that has been developed for determination whether the chemical substance produced the inhibition is a new A.B. or a known compound. This assay employs paper or TLC and biologic assay. 6. The extract containing the newly discovered A.B. is chromatographed along with reference in different solvent systems. This would indicate the newly discovered A.B. was a known compound or not.. Antibiotics Detection of A.B. on chromatogram : Chemical methods for detection is impossible and difficult, so that we depend on the biologic method by placing the developed chromatogram on an agar medium that has been seeded with an appropriate test organism, the A.B. diffuse from the chromatogram in to the agar and after incubation , clear zone on the agar owing to inhibition of growth of the test organism indicate the posion of the A.B. on chromatogram. Antibiotics Generally, planar chromatographic, viz. TLC and PC are used for bioautography, but the detection method can be successfully improved by the application of advanced chromatographic tools, namely, high performance thin layer chromatography (HPTLC), over-pressured layer chromatography (OPLC), and planar electro chromatography (PLC). Antibiotics Commercial production Antibiotics Commercial production: Antibiotics are produced industrially by a process of fermentation, where the source microorganism is grown in large containers (100,000–150,000 liters or more) containing a liquid growth medium. Oxygen concentration, temperature, pH and nutrient levels must be optimal, and are closely monitored and adjusted if necessary. As antibiotics aresecondary metabolites, the population size must be controlled very carefully to ensure that maximum yield is obtained before the cells die. Antibiotics Once the process is complete, the antibiotic must be extracted and purified to a crystalline product. This is easier to achieve if the antibiotic is soluble in organic solvent. Otherwise it must first be removed by ion exchange, adsorption or chemical precipitation. Strains used for production microorganisms used in fermentation are rarely identical to the wild type. This is because species are often genetically modified to yield the maximum amounts of antibiotics. Antibiotics Mutation is often used, and is encouraged by introducing mutagens such as ultraviolet radiation, x-rays or certain chemicals. Selection and further reproduction of the higher yielding strains over many generations can raise yields by 20-fold or more. Another technique used to increase yields is gene amplification, where copies of genes coding for enzymes involved in the antibiotic production can be inserted back into a cell, via vectors such as plasmids. This process must be closely linked with retesting of antibiotic production. Antibiotics Mechanisms of action : 1. Inhibit cell wall synthesis. 2. Inhibit protein synthesis. 3. Inhibit nucleic acid synthesis. 4. Injury to plasma membrane. 5. Inhibit synthesis of essential metabolites. Antibiotics Antibiotics A. Inhibitors of cell wall synthesis 1. Penicillins 2. Cephalosporins 3. Other antibacterial agents that act on cell walls B. Disrupters of cell membranes 1. Polymyxins 2. Tyrocidins Antibiotics C. Inhibitors of protein synthesis 1. Aminoglycosides 2. Tetracyclines 3. Chloramphenicol 4. Other antibacterial agents that affect protein synthesis a. Macrolides b. Lincosamides Antibiotics D. Inhibitors of nucleic acid synthesis 1. Rifampin 2. Quinolones E. Antimetabolites and other antibacterial agents 1. Sulfonamides 2. Isoniazid 3. Ethambutol 4. Nitrofurans Antibiotics Mode of Resistance : 1. Enzymatic inactivation. 2. Altered permeability of the pathogen to the A.B. 3. Development of altered , less sensitive enzymes or of alternate metabolic pathways in the pathogen. Antibiotics Classification of antibiotics according to the biosynthetic pathways : 1. Antibiotics derived from amino acids metabolisms. 2. antibiotics derived from acetate metabolism. 3. antibiotics derived from carbohydrate metabolism.