HistoryHistoryChemotherapy as a science began with

Paul EhrlichPaul Ehrlich in the first decade of last century.

Ehrlich received the Nobel Prize Nobel Prize for Medicine in 1908 1908.

In 19061906 he discovered the structural formula of atoxylatoxyl, a chemical compound which had been shown to be able to treat sleeping sickness sleeping sickness (trypanosomiasis).

In 19091909 he and his student Sahachiro Sahachiro Hata Hata developed Salvarsan Salvarsan (arsphenamine), a treatment effective against syphilis.

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Gerhard Domagk Gerhard Domagk was a German pathologist and bacteriologist recognized with the discovery of the first commercially available antibiotic (marketed under the brand (marketed under the brand name Prontosil)name Prontosil).

In 19391939, he received the Nobel Prize Nobel Prize in Medicine for this discovery, the first drug effective against bacterial infections (streptococcalstreptococcal infections ).

ProntosilProntosil decomposes in the living body to give a highly active active sulphonamide sulphonamide and the toxictoxic compound thiaminobenzenethiaminobenzene.

The 'golden age' of antimicrobial therapy began with the production of penicillinpenicillin.

This was discovered by Sir Alexander Fleming (1929) Sir Alexander Fleming (1929) who noticed that the growth of staphylococcistaphylococci was inhibited round a mould of Penicilian Penicilian notatum notatum which was growing by accident on a culture plate.

From this mould, penicillin was extracted and mass produced in 19401940 by the work of Florey Florey && ChainChain.

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• He shared the Nobel Prize in Physiology or Medicine in 1945 with Howard Florey and Ernst Chain.

Antibiotics =Antibiotics = a natural substance produced by

a micro-organism to kill another.

Anti-infectives / Anti-microbrial = Anti-infectives / Anti-microbrial = any agent (natural or

synthetic) that kills pathogens (microbes).

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Classification of Classification of antibiotics antibiotics l antibacterialantibacterial

According to their origin

(sources)

Microorganisms

Synthetic antibiotics

Semi synthetic

antibiotics

Bacteria

Fungi

Streptomyces spp

Examples of Microbial Sources of Antibiotics

StreptomycesStreptomyces

• Streptomyces is the largest genus of Actinobacteria. • Over 500 species of Streptomyces bacteria have been described.

According to their

chemical structure

a. Beta-lactam antibiotics b. Aminoglycosides

c. Aminocyclitols d. Tetracyclines

e. Polyenes f. Macrolides

β-Lactam antibiotics β-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contains a β-a β-Lactam nucleus Lactam nucleus in its molecular structure.

It includes penicillins, cephalosporins, and cephmycins.

a. Beta-lactam antibiotics

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An aminoglycoside is a molecule or a portion of a molecule composed of amino-modified sugars.

They are glycosidic derivatives of streptamine.

Both streptomycin and dihydrostreptomycin contain streptidin and aminosugars in their structure, while other members containing deoxystreptamine and amino sugar in their structure e.g. neomycin, kanamycin, tobramycin, amikacin, and gentamicin.

Aminoglycosides that are derived from bacteria of the StreptomycesStreptomyces genus are named with the suffix -mycinmycin,, whereas those that are derived from MicromonosporaMicromonospora are named with the suffix –micinmicin..

b. Aminoglycosides

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It is a closely related closely related group to aminoglycosidesaminoglycosides.

These contain no amino sugar no amino sugar in their structure e.g. spectinomycin.

c. Aminocyclitols

A family of closely related antibiotics with four-ringed four-ringed structurestructure e.g. tetracycline, chlorotetracycline, oxytetracycline, demeclocycline, methacycline, doxycycline and minocycline.

d. Tetracyclines

These are characterized by possessing a large ring a large ring containing a lactone group and a hydrophobic regionlactone group and a hydrophobic region consisting of a sequence of 4-7 conjugated double sequence of 4-7 conjugated double bonds. bonds.

Polyenes are poly-unsaturated organic compounds that contain one or more sequences of alternating double and single carbon-carbon bonds, e.g. nstatin, nstatin, amphotericin.amphotericin.

e. Polyenes

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These consisting of a macrocyclic lactone macrocyclic lactone ring to which sugars are attached.

They include erythromycinerythromycin, oleandomycinoleandomycin and spiramycinspiramycin.

f. Macrolides

According to the spectrum of

their biological action

a. Antibacterial antibiotics b. Antifungal antibiotics

c. Antitumor antibiotics d. Antiprotozoal antibiotics

e. Antiviral antibiotics

a. Antibacterial antibiotics

Narrow spectrum

Broad spectrum

Tuberculostatic

Natural penicillins and erythromycin (G +ve) Polymyxin (G –ve).

Effective against at least some members of most genera

Tetracyclines and chloramphenicol.

Streptomycin, kanamycin and cycloserine.

b. Antifungal antibiotics

c. Antitumor antibiotics

d. Antiprotozoal antibiotics

e. Antiviral antibiotics

Nystatin, amphotericin B,

griseofulvin, and candicin.

Actinomycins, mitomycins.

Fumagillin.

Helinine.

According to their mode of

action

a. Inhibitors of cell wall synthesis

.b. Antibiotics acting on cell

membranes

c. Inhibitors of protein synthesis

d. Inhibitors of nucleic acid synthesis

e. Inhibitors of folic acid synthesis (antifolates)

a. Inhibitors of cell wall synthesis

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The steps of biosynthesis involves many essential

enzymes:

I. RacemesRacemes (catalyze change of L-alanine to D-alanine).

II. SynthetaseSynthetase (join two D-alanine molecules forming the

terminal D-alanyl-D-alanineD-alanyl-D-alanine residue of the penta

peptide).

III. TranspeptidasesTranspeptidases (catalyze transpeptidation or cross-

linking reactions).

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Penicillins.Penicillins.

Cephalosporins.Cephalosporins.

Bacitracin.Bacitracin.

Vancomycin.Vancomycin.

Teicoplanin. Teicoplanin.

Cycloserine.Cycloserine.

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