Natural antibiotics III By : Noor hisham Al Atraqchi M.Sc. pharmacognosy

Macrolides Macrolide antibiotics are typically characterized by macrocyclic lactones having a ring-size ranging between 12-16 atoms and also possess inherent extensive branching through the methyl substituents. However, the macrolactone ring essentially bears a glycosidal linkage to either one or several sugar functions. The various important members of ‘macrolide antibiotics’ are, namely: Erythromycin, Clarithromycin, Arithromycin, Troleandomycin; Spiramycins.

Macrolides MOA: The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting translocation steps of protein synthesis. In general, these antibiotics essentially exhibit a narrow spectrum of antibacterial activity, most importantly against the Gram-positive microorganisms. It is, however the antibacterial spectrum of the macrolides resembles, but is not very much identical to, that of the penicillins; hence, they are valuable alternative or substitute for such patients who are found to be allergic to the penicillins.

Erythromycin Biological Sources : It is produced by cultures Streptomyces erythreus . Waksman and Henrici were the pioneer in finding this antibiotic in a soil sample collected from the Philippine. Erythromycin is, in fact, a mixture containing principally Erythromycin A. Together with small quantum of Erythromycins B and C.

Uses It is found to be most effective against Gram-positive cocci. A low concentration of erythromycin also inhibit mycoplasma and the agent of Legionnaire’s disease. It inhibits the spirochaete Treponema pallidum and is an alternative to penicillin in the treatment of syphilis. It is quite often regarded as the ‘drug-of-choice’ for undiagnosed pneumonias. It is extensively employed as an alternative to b-lactam antibiotics in soft-tissue infections, skin and in respiratory related diseases particularly in penicillin-allergic patients.

Aminoglycosides Biological sources : Aminoglycosides are derived from either Streptomyces species or Micromonospora species. The term “aminoglycoside” stems from their structure—two amino sugars joined by a glycosidic linkage to a central hexose nucleus. MOA: they inhibit protein synthesis by binding to the 30S ribosomal subunit, where they interfere with assembly of the functional ribosomal apparatus and/or cause the 30S subunit of the completed ribosome to misread the genetic code

The major spectrum of activity of the aminoglycosides essentially comprise of aerobic Gram-negative bacilli and Staphylococcus aurous. The aminoglycoside antibiotics include the following members : Amikacin, Gentamycin, Paramycin, kanamycin, Netilmicin, Streptomycin Tobramycin

Gentamycin Biological Sources :It is an antibiotic complex produced by the fermentation of Micromonospora purpurea and M. echinospora. Uses It is currently the most important drug of choice for the treatment of infections caused by most aerobic Gram-negative bacteria, besides several strains of Staphylococci. 2. It essentially exhibits a broad-spectrum antibacterial activity. 3. It is found to be specifically effective against Pseudomonas, because species of this genus resistant to ‘other antibiotics’ have proved to be an important cause of surgical infections. 4. It is employed topically in the treatment of impetigo, infected bed sores, burns and also in the infections of external-eye.

Streptomycin Biological Sources : Streptomycin was obtained from a strain of Streptomyces griseus and produced by the soil Actinomycete. Uses 1. It is a potent antibacterial, and more so as a tuberculosstatic agent. 2. Streptomycin exerts its action in the control and management of Yersinia pestis (plague) and tularemia. 3- streptomycin-penicillin used for endocarditis*; and streptomycin- tetracyclin employed for brucellosis. 4. Streptomycin exerts bacteriostatic action in low concentrations and bactericidal in high concentrations to a good number of Gram-negative and Gram-positive microorganisms. Note: The incidence of serious auditory impairment is now recognized

Tetracyclines The tetracyclines are group of broad spectrum orally active actinomycete antibiotics produced by cultures of Streptomyces species, and possessing appreciable therapeutic value. Chlortetracycline was the first member of this group isolated from Streptomyces aureofaciens in 1948. . MOA: the drugs bind reversibly to the 30S subunit of the bacterial ribosome. This action prevents binding of tRNA to the mRNA– ribosome complex, thereby inhibiting bacterial protein synthesis ‘methylation’ and ‘chlorination’ procedures have resulted in the fermentative production of a good number of tetracycline variants, namely: demeclocycline, methacycline, doxycycline, minocycline, lymecycline

Tetracycline Biological Source: It is obtained from Streptomyces species cultured in an appropriate nutrient medium. Preparation: It may be prepared by removal of chlorine from chlortetracycline and subjecting it to hydrogenation. Uses Tetracyclines are generally used in the treatment of infections of the urinary tract and the intestines used in the treatment of infections caused by chlamydia, especially in patients allergic to β- lactams and macrolides. However, their use for these indications has decreased due to widespread development of drug resistance to these compounds. Their most common current use is in the treatment of moderately severe acne and rosacea. In addition, they may be used to treat Legionnaires’ disease.

Polypeptide Antibiotics A group of polypeptides of bacterial origin that are found to comprise of D- and L-amino acids, do exert a marked and pronounced antibiotic activity. These specific antibiotics have two inherent major anomalies, namely: first, very poor absorption from the intestinal tract; and secondly, possess high degree of nephrotoxicity when used systemically. Generally, the polypeptide antibiotics exert a predominantly Gram- positive spectrum; however, there are a few-exceptions that are solely active against Gram-negative organisms, such as: the strongly basic polymyxins. The various important members of ‘polypeptide antibiotics’ are, namely: cycloserine; polymyxin-B; colistin (polymixin-E), bacitrasin; Teichoplanin

Polymyxin B Biological Source: Polymyxins represent a group of cycle polypeptide antibiotics produced by various species of Bacillus. However, polymyxins A to E were primarily isolated from Bacillus polymyxa . MOA: Polypeptide antibiotics act by binding to phospholipids on the bacterial cell membrane of gram-negative bacteria. They have a detergent-like effect that disrupts cell membrane integrity, leading to leakage of cellular components and ultimately cell death.

uses It is used topically in ointments (usually 5000 or 10,000 Units/g) and ophthalmic solutions (10,000 Units/ml). It is used topically either for the treatment or the prevention and treatment of external ocular infections caused by susceptible microorganisms, especially Ps aeruginosa.