Macrolidebased

Macrolide-based compounds are molecules featuring a macrocyclic lactone ring as the central scaffold, typically bearing deoxy sugars such as desosamine and cladinose. The best-known examples are macrolide antibiotics produced by actinomycetes (notably Saccharopolyspora erythraea) and later modified synthetically. The macrocycle usually contains 12 to 16 members, and small changes influence spectrum, potency, and pharmacokinetics.

They bind reversibly to the 50S ribosomal subunit, blocking translocation during protein synthesis. Most macrolide-based agents are bacteriostatic, though some exhibit bactericidal activity against specific organisms. They are active against many Gram-positive bacteria and atypical pathogens such as Mycoplasma and Legionella, with newer members offering improved tissue penetration and longer half-lives.

Erythromycin is acid-labile with limited oral bioavailability, while azithromycin and clarithromycin are more acid-stable with longer half-lives. Clinically, macrolide-based drugs treat respiratory tract infections, skin and soft-tissue infections, and several sexually transmitted and atypical pneumonias. They can also have anti-inflammatory effects in certain conditions.

Resistance commonly arises from methylation of the 23S rRNA binding site by erm genes, efflux pumps, or inactivating enzymes. Cross-resistance with lincosamides and streptogramins can occur. Adverse effects include gastrointestinal disturbance and hepatotoxicity; some macrolides can prolong the QT interval and interact with other medications.

The macrolide-based scaffold has inspired macrocyclic lactone drugs beyond antibiotics, and remains a focus of natural-product and medicinal chemistry, with ongoing work to broaden spectrum, reduce resistance, and improve safety.