Chemistry and SAR of Aminoglycosides

Views:
 
     
 

Presentation Description

The PPT describes about the chemical aspects of aminoglycoside including their mode of action, uses and SAR.

Comments

Presentation Transcript

PowerPoint Presentation:

AMINOGLYCOSIDES By- Gaurav Kayal ( M.Pharm ) Assistant Professor (Pharmaceutical Chemistry)

PowerPoint Presentation:

Contents Introduction Structure Streptomycin SAR Spectrum of activity Mechanism of action Uses

PowerPoint Presentation:

By Gaurav Kayal

PowerPoint Presentation:

The aminoglycoside class of antibiotics contains a pharmacophoric 1,3-diaminoinositol derivatives Streptamine 2-Deoxystreptamine Spectinamine By Gaurav Kayal Introduction

PowerPoint Presentation:

Aminoglycosides are so named because their structures consist of amino sugars linked glycosidically. All have at least one aminohexose, and some have a pentose lacking an amino group. ( L- Streptose ) ( Streptide ) ( N-Methyl-L-Glucosamine ) By Gaurav Kayal Structure

PowerPoint Presentation:

Aminoglycosides are strong basic compounds that exist as polycations at physiological p H. Their inorganic acid salts are very soluble in water. All are available as sulfates. The high water solubility of the aminoglycosides no doubt contributes to their pharmacokinetic properties. They distribute well into most body fluids but not into the ventral nervous system, bone, or fatty or connective tissues. They tend to concentrate in the kidneys and excreted by glomerular filtration. Aminoglycosides are apparently not metabolized in vivo. By Gaurav Kayal

PowerPoint Presentation:

It should be remember that penicillin and aminoglycoside antibiotics must never be physically mixed , because both are chemically inactivated to a significant degree on mixing . By Gaurav Kayal

PowerPoint Presentation:

Streptomycin Streptomycin is the first aminoglycosides isolated from Streptomyces griseus . There are three basic centers in the structure. By Gaurav Kayal Ring I Ring II Ring III

PowerPoint Presentation:

Structure Activity Relationship (SAR): By Gaurav Kayal Ring I: It is important for broad spectrum anti-bacterial activity. 2’, 6’ amino functional group are important for activity. Methylation at 6’ amino or methylation at 6’ C does not lowers the activity. It also confers resistence to enzymatic acylation on 6’ amino group. rRemoval of 3 rd position OH or 4’-OH group both in Kanamycin structure does not lwers the activity. 3’4’ deoxy kanamycin (Dubekacin) is also potent. Gentamycin series lacks ‘O’ functional group at 3’4’ position, still the compounds are active. Sisomycin, Netilmycin have double bond between 4’5’ position atrre not activated by phosphotranseferase enzyme.

PowerPoint Presentation:

Structure Activity Relationship (SAR): By Gaurav Kayal Ring II: Very few structural modifications are tlerated in Ring II. 1 st position amino group can be acylated i.e., Amikacin largely retains activity. Netilmycin, 1-N-ethyl sisomycin retain activity in addition provide resistance to bacterial inactivating enzyme. Ring III: Functional groups of ring III are less susceptible to structural changes than ring I and II. 2’’ deoxy Gentamycin is significantly less active than 2 amino derivatives of Seldomycin. 3’’ amino group of gentamycin may be primarily or secondarily substituted have higher activity. 4’’ OH either axial or equatorial- little variation in activity.

Spectrum of activity :

Spectrum of activity Aminoglycosides are used for treatment of serious systemic infections caused by aerobic Gram-negative bacilli. Aerobic G-N and G-P cocci tend to be less sensitive; thus the β –lactams and other antibiotics tend to be preferred for the treatment of infections caused by these organisms. Anaerobic bacteria are invariably resistant to the aminoglycosides. Streptomycin is the most effective of the group for the chemotherapy of tuberculosis. Under certain circumstances, aminoglycoside and β –lactams antibiotics exert a synergistic action in vivo against some bacterial strains when the two are administered jointly. By Gaurav Kayal

Mechanism of Action :

Mechanism of Action The mechanism of action of these antibiotics believed that they can inhibit the biosynthesis of protein of bacteria. At less than toxic doses, they bind to the protein portion of the 30S ribosomal subunit leading to mistranslation of RNA templates and the consequent insertion and wrong amino acids and formation so-called nonsense proteins. By Gaurav Kayal

PowerPoint Presentation:

By Gaurav Kayal

Uses::

Uses: Streptomycin was the first aminoglycoside isolated and the first antibiotic with potent activity against Mycobacterium tuberculosis and this antibiotic continues to be used to treat tuberculosis, but as a result of the development of resistance, now in combination therapy with other antibiotics. Streptomycin can also be used for the treatment of tularemia, plague and leprosy. The aminoglycosides are highly water soluble and poorly absorbed orally. These antibiotics are therefore primarily delivered by intramuscular injection or intravenously. By Gaurav Kayal

PowerPoint Presentation:

THANK YOU For Doubts/ Queries- Mr. Gaurav Kayal Assistant Professor (Pharmaceutical Chemistry) (Ph-9009991186, [email protected])

authorStream Live Help