Antibiotic - Nely.pdf

FARMAKOGNOSI 2 ANTIBIOTIC

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Definisi “Anti – Biotika “  anti kehidupan Senyawa kimia yang dihasilkan oleh mikroorganisme tertentu yang memiliki kemampuan (dalam konsentrasi rendah) untuk menghambat atau membunuh secara selektif mikroorganisme lain.

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• Senyawa sintetik • Senyawa yg diisolasi dari tanaman tinggi

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HISTORY

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Microbial Sources of Antibiotics Microorganism

Antibiotics

Gram-Positive Rods Bacillus subtilis

Bacitracin

Bacillus polymyxa

Polymyxin

Fungi Cephalosporium spp

Cephalothin

Penicillium griseofulvum

Griseofulvin

Penicillium notatum

Penicillin

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Microbial Sources of Antibiotics Microorganism

Antibiotics

Uses

Ampotericin B

Anti fungi

Chloramphenicol

S. Thypii

Chlortetracycline and tetracycline

Broad spect

Actinomycetes Streptomyces

nodosus S. venezuelae S. aureofaciens S. erythraeus S. fradiae S. lincolnensis S. antibioticus

Erythromycin Streptomycin Lincomycin  Clindamycin (semi sintetik) Dactinomycin = Anctinomycin D

Micromonospor Gentamicin

a purpureae [email protected]

Anti cancer Broad spect

Non Microbial Sources of Antibiotics Sources

Antimicrobial activity

Linchen

Usnic acid and Vulpinic acid (bakteriostatik dan antifungi)

Monocotyledon

Aliin (Allium sativum)

Dicotyledon

Senyawa carvacrol (Thymus vulgaris) Tea tree oil (Melaleucae alternifolia) Cannabidiol and tetrahydrocannabinol (Cannabis sativa)

Marine Organism

Cephalosporin C (Cephalosporium acremonium) Istamycin A and B (Streptomycete) Bromin compound (red algae) [email protected]

terinduksi spontan

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New Antibiotics

COMMERCIAL PRODUCTION

1. Fermentation process  screening new antibiotics  soil  source of microorganims 2. Semi synthetic process  modified from isolate 3. Syntetic process [email protected]

Natural – Derived from natural sources such as fungi and soil bacteria. Penicillin as the classic example, derived from the fungus Penicillium Pharmaceutical industry produces penicillin from cultures of Penicillium chrysogenum that are adapted for high yield Others: many aminoglycosides from soil bacteria (e.g., streptomycin) Semi-synthetic - Natural products that have been chemically modified to improve effectiveness of the product or to reduce side effects, etc Examples include the β-lactams ampicillin, amoxicillin, etc, derived from fungi Completely synthetic – Products are synthesized completely in the laboratory Sulfa drugs, folic acid analogs are examples [email protected]

MODES AND MECHANISM OF ACTION

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ANTIBIOTIC DERIVED FROM AMINO ACID METABOLISM • Penicillin • Cephalosporin  Cephalosporium acremonium • Chloramphenicol  Streptomyces • Cycloserine • Dactinomycin • Antibiotic polypetide : bacitracin, polymixin [email protected]

Synthesis of penicillins by fermentation Penicillin

Tidak aktif secara biologik [email protected]

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Sifat – sifat penicilin • Inti -laktam yang tergabung pada cincin thiazolidin • Kerusakan pada cincin -laktam atau thiazolidin  kehilangan aktivitas antimikroba • -laktam  labil secara biologik dan kimia • Tidak tahan asam pH < 5  asam penillic (inactive) pH > 5  asam penicilloic (inactive) [email protected]

Resistensi Penicillin

• Mikroorganisme memproduksi -laktamase (penicillase) • Pengatasan  dikembangkan penicillin yang stabil dengan pH lambung dan tahan terhadap laktamase (penicillase) [email protected]

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Cephalosporin • Cephalosporium acremonium • isolation of three‘antibiotic substances’ from the culture of this specific organism : 1. Cephalosporin P (little therapeutic significance), 2. Penicillin N (originally termed as cephalosporin N) obtained as the major component and differs significantly from the common penicillin by its antibacterial activity and hydrophilic character; 3. Cephalosporin C showed low toxicity and in vitroactivity against the penicillin-resistant Staphylococci. [email protected]

• • • •

1. 2. 3. 4.

First generation : Cefalexin, Cefradine, Cefadroxil Second generation : Cefaclor, ceprozil, cefamandole Third generation : ceftazidime, ceftriaxone, ceixime Four generation [email protected]

ANTIBIOTICS DERIVED FROM ACETATE METABOLISM • • • •

Tetracycline Macrolide Polyene Griseofulvin

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Biosintesa Tetracycline • Antibiotika golongan actinomycetes • Jalur metabolisme acetat-malonat • Primer : malonamylcoA • 8 unit malonat mengalami kondensasi secara bertahap dg penambahan unit C2 dan dekarboksilasi  C 19 (poliketida linier) [email protected]

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ANTIBIOTICS DERIVED ROM CARBOHYDRATE METABOLISM • • • • • • •

Gentamycin Kanamycin Neomycin Streptomycin Tobramycin Paromomycin Spectinomycin [email protected]

Aminoglycosides • The aminoglycosides each contain one or more amino sugars, for instance: neosamine or glucosamine, bridged by glycoside linkages to a basic, either amino or guanidino, sixmembered carbon ring, such as: streptamine or streptidine as given below:

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Tugas Baca • Bacalah materi kuliah dari buku dari buku “pharmacognocy by ashuthos Kar” • Buatlah MindMap • 1. “Screening of newer antibiotic” (untuk memudahkan pemahaman lihat video yang sudah diupload) • 2. Large-scale production • 3. Phases in fermentative process • 4. Separation and isolation of antibiotics • Tugas dikerjakan perkelompok untuk minggu depan • 1 kelompok terdiri atas 5-6 anggota • Presentasi kelompok

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