Macrolides - Medicinal Chemistry III B. Pharma 6th Semester



• Macrolides - Introduction

• Chemistry of Macrolides

• Over view of Mechanism of action and Resistance of Macrolides

• Spectrum of Activity of Macrolides

• Study of Individual products

Learning Objectives

At the end of this lecture, student will be able to

• Discuss the chemistry of Macrolides

• Explain the mode of action and resistance of Macrolides

• Outline the spectrum of activity of Macrolides

• Discuss the structural features of Macrolides and uses


• Macrolides are the antibiotics isolated from the Actinomycetes.

• Picromycin is the first compound of this group identified as ‘Macrolide’.

• Others in the sequence are erythromycin and carbomycin and then other macrolides like azithromycin, clarothromycin and oleandomycin.


3 common chemical characteristics

• A large lactone ring (i.e., why the name macrolide)

• A ketone group

• A glycosidically linked amino sugar

• The  lactone  ring  has  12,  14  or  16  atoms  in  it  and  it  is  often unsaturated with an olefinic group conjugated with the ketone function.

• In  addition,  to  the  amino  sugar,  a  neutral  sugar  that  is  linked glycosidically to the lactone ring may be present eg., Erythromycin

• They are stable in aqueous solutions at or below room temperature but are inactivated by acids, bases and heat.

• Macrolides are bases that form salts with pKa values between 6.0 and 9.0, because of the dimethyl amino group on the sugar moiety.



Mechanism of action


• It binds selectively to specific site on the 50S ribosomal subunit to prevent the translocation step of bacterial protein synthesis

• It does not bind to mammalian ribosomes and so will not affect the protein synthesis in mammalian cells

Mechanism of Resistance

• The nonspecific resistance to the antibacterial action of erythromycin among many species of Gram-ve bacilli is largely related to the inability of the antibiotic to penetrate the cell walls of these organisms. Protoplasts from Gram –Ve bacilli which lack cell walls are sensitive to erythromycin.

• A highly specific resistance mechanism to the macrolide antibiotics occurs in    erythromycin-resistant strains of S.aureus. These strains produce an enzyme that methylates a specific residue at the erythromycin-binding site of the bacterial 50S ribosomal subunit. The methylated ribisomal RNA remains active in protein synthesis but no longer binds erythromycin.

Spectrum of activity

The spectrum of antibacterial activity of the more potent macrolides, as erythromycin resembles that of penicillin.

They are active against bacterial strains that are resistant to the penicillins

Effective against most species of Gram+ve bacteria-both cocci & bacilli, some Gram-ve cocci especially Neisseria species, Treponema pallidum, etc.

In contrast to penicillins, they are effective against Mycoplasma, Chlamydia, Campylobacter and Legionella species, some strains of H. influenzae and Brucella species.


Isolated from S.erythraceus

• It is a well-tolerated antibiotic

• Used in the treatment of upper respiratory and soft-tissue infections caused by Gram+ve bacteria.

• Effective against many venereal diseases including gonorrhea and syphilis

• Useful alternative for the treatment of many infections in patients allergic to penicillins.

• Erythromycin was shown to be effective therapy for Eaton agent pneumonia (Mycoplasma pneumoniae), venereal diseases caused by Chlamydia, bacterial enteritis caused by Campylobacter jejuni, and Legionnaires disease


• Clarithromycin is well absorbed following oral administration

• Some of the microbiological properties of clarithromycin also appear to be superior to those of erythromycin

• It exhibits greater potency against M. pneumoniae, Legionella spp., Chlamydia pneumoniae, H. influenzae, and M. catarrhalis than does erythromycin

• Activity against unusual pathogens such as Borrelia burgdorferi (the cause of Lyme disease) and the Mycobacterium avium complex (MAC)


• It’s more active against gram-ve organisms (including H. influenza) than against Gram+ve organisms

• Highly active against intracellular pathogens as Mycoplasma, Chlamydia, Legionella & Salmonella

• Oral bioavailability is good if administered 1-2 hours before food as food decreases its absorption

• Its greater activity coupled with its extended half-life permits a five day dosing schedule for upper respiratory tract infections

• Use: to treat upper & lower resp. tract infections, skin and soft tissue infections, urogenital infections including Gonnorrhea.

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