Penicillin Antibiotics: Mechanism, Structure and Types
What are penicillin antibiotics?
Penicillin is a class of antibiotics containing penicillanes in the molecule, which can destroy the cell wall of bacteria and play a bactericidal role in the breeding period of bacterial cells. It is an antibiotic extracted from penicillium (mainly P. chrysogenum and P. rubens). It was first discovered experimentally by Scottish scientist Alexander Fleming in 1928, when he noticed that penicillium notatum was able to secrete a substance that effectively inhibited the growth of staphylococcus. However, the development of penicillin as a drug went through a long process and was not used in mass production until the 1940s.
Penicillin is an organic acid that is difficult to dissolve in water. The amide bond (-CO-NH-) in it is easily decomposed by acids, bases, heavy metal ions, penicillin enzymes, etc. and becomes ineffective. The sodium salt or potassium salt corresponding to penicillin is a white crystalline powder, odorless, hygroscopic, easily soluble in water, physiological saline or glucose solution, and slightly soluble in ethanol. The sodium salt and potassium salt corresponding to penicillin are commonly used in clinical practice. However, because the aqueous solution of potassium salt and sodium salt is unstable and its potency quickly decreases at room temperature, it should be prepared and used immediately. When stored, it should be stored in a refrigerator. Refrigerated.
Mechanism of action of penicillin
Penicillin is a beta-lactam antibiotic that competes with bacteria for mucopeptide synthesises (enzymes involved in bacterial synthesis of cell walls), called penicillin binding proteins (PBPs). When beta-lactam antibacterial drugs bind to penicillin binding protein, the penicillin binding protein loses its enzyme activity, further interferes with the synthesis of bacterial cell wall, causing bacterial cell wall defects, a large amount of water flooding into the bacterial body, eventually causing cell lysis and bacterial death.
Structure of penicillin
Amide: Involved in the stability of the molecule and its interaction with bacterial enzymes.
cis stereochemistry: The specific spatial arrangement of atoms around the β-lactam ring allows the molecule to be correctly inserted into the active sites of bacterial enzymes such as PBPs that are targeted by antibiotics.
Lactam ring: The β-lactam ring is a four-membered lactam ring (i.e. cyclic amide) that is the most critical part of the molecule and inhibits the synthesis of bacterial cell walls.
Bicyclic system: In the structure of β-lactam antibiotics, the bicyclic system includes a four-membered β-lactam ring and a five-membered thiazolidine ring or other similar five-membered rings. It is one of the key structures of β-lactam antibiotics and is involved in the stability of the molecule and its binding to bacterial enzymes.
Free carboxylate: Related to the location and mechanism of action of the molecule in the organism, and often interacts with the binding site of the enzyme.
Variable R groups: Changes in the R group are used to develop new antibiotics with different antibacterial spectra or improved drug properties such as acid resistance or enzymatic degradation resistance.
Types of penicillin
Penicillin was used in clinical practice in the early 1940s. After conducting a lot of research on penicillin, some penicillin was discovered. When people chemically modified penicillin, some effective semi-synthetic penicillin was obtained. In the 1970s, some penicillin with parent nuclei similar to penicillin and also containing a β-lactam ring, but not a tetrahydrothiazole ring structure, can be divided into three generations:
Penicillin antibiotics at BOC Sciences
First-generation penicillin refers to natural penicillin, such as penicillin G (benzylpenicillin) and penicillin V. Penicillin G is a narrow-spectrum antibiotic mainly used to treat infections caused by susceptible bacteria. The R group of penicillin G is a benzoyl group (-C6H5-CO-). The benzoyl group affects the electronic distribution and spatial structure of the entire molecule, allowing penicillin G to effectively bind to bacterial PBPs, thereby inhibiting bacterial cell wall synthesis. At the same time, benzoyl groups make penicillin G unstable in gastric acid and easily degraded by the acidic environment. Penicillin V is a phenoxymethyl analogue of penicillin G. The R group of penicillin V is a phenoxymethyl group (-OCH2-C6H5), making penicillin V resistant to gastric acid.
The second-generation penicillin refers to semi-synthetic penicillin obtained by using the penicillin parent nucleus-6-aminopenicillanic acid (6-APA) to change the side chain, such as methicillin, carbenicillin, and ampicillin.
The third-generation penicillin has the same beta-lactam ring as penicillin in its parent core structure, but does not have a tetrahydrothiazole ring, such as thiomycin and nocarmycin.
Chemical structure diagram of common penicillin.
According to its characteristics, penicillin can be divided into:
Penicillin G: Such as penicillin G potassium, penicillin G sodium, long-acting penicillin.
Penicillin V: Also known as phenoxymethylpenicillin, 6-phenoxyacetamidopenicillanic acid, such as penicillin V potassium.
Enzyme resistant penicillin: Such as oxacillin, cloxacillin.
Broad-spectrum penicillin: Such as ampicillin, amoxicillin.
Broad-spectrum penicillin against Pseudomonas aeruginosa: Such as carbenicillin, piperazillin, furbenicillin.
Azamicillin: Such as methicillin and its ester, pimecillin, etc., are characterized by relatively enzyme resistance and are effective against certain negative bacteria (such as colon, Klebsiella and Salmonella), but are poorly effective against Pseudomonas aeruginosa.
Penicillin derivatives
Natural penicillin is a weak acid substance with multiple carboxyl functional groups in its molecule. It is prone to ionization reactions or rearrangement reactions in water and loses its antibacterial activity. Therefore, the carboxyl groups of penicillin are often used to react with alcohol substances to make it produce a relatively stable esterification product. Common reactions related to penicillin include the following two:
Esterification reaction with hydrochloric acid: Penicillin G sodium salt reacts with hydrochloric acid to obtain penicillin hydrochloride. During this process, hydrochloric acid serves as an esterification reagent and reacts with the carboxyl group in the penicillin molecule to form an ester bond.
Acylation reaction with amino acids: The carbonyl group (C=O) on the β-lactam ring of penicillin can form an acyl group combined with the nitrogen atom in the amino acid, and an acylation reaction occurs to form an acylated derivative of penicillin. These acylated derivatives have better pharmacological properties and a broader antibacterial spectrum. Common acylated derivatives include propionylated penicillin (C16H19N2NaO5S) and phenylacetylated penicillin (C22H24N2O9S).
Application of penicillin
Penicillin is a widely used antibiotic mainly used to treat various infections caused by sensitive bacteria. The following are the main clinical applications of penicillin:
Respiratory infections: Penicillin is the drug of choice for the treatment of respiratory infections caused by Streptococcus pneumoniae and hemolytic Streptococcus. It can also be used to treat respiratory infections caused by other bacteria such as diphtheria.
Skin and soft tissue infections: Penicillin can be used to treat skin and soft tissue infections caused by Staphylococcus aureus, Streptococcus, etc., such as impetigo, cellulitis, etc.
Urogenital tract infections: Penicillin can be used to treat urogenital infections such as urethritis, cystitis, and prostatitis caused by Escherichia coli and Staphylococcus.
Bone and joint infections: Penicillin can be used to treat bone and joint infections caused by Staphylococcus aureus, hemolytic streptococcus.
Cardiovascular infections: Penicillin can be used to treat cardiovascular infections caused by streptococci, staphylococci, such as endocarditis.
Nervous system infections: Penicillin can be used to treat nervous system infections caused by meningococcus, such as meningitis.
