The history of the tetracyclines involves the collective contributions of thousands of dedicated researchers, scientists,
clinicians, and business executives over the course of more than 60 years. Discovered as natural products
from actinomycetes soil bacteria, the tetracyclines were first reported in the scientific literature in 1948. They were
noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in
the late 1940s to the early 1950s. The second-generation semisynthetic analogs and more recent third-generation
compounds show the continued evolution of the tetracycline scaffold toward derivatives with increased potency
aswell as efficacy against tetracycline-resistant bacteria,with improved pharmacokinetic and chemical properties.
Their biologic activity against a wide spectrum of microbial pathogens and their uses in mammalian models of
inflammation, neurodegeneration, and other biological systems indicate that the tetracyclines will continue to be
successful therapeutics in infectiousdiseases andas potential therapeutics againstinflammation-basedmammalian
cell diseases.