Testolactone: The Rise and Fall of a Drug

Abstract

Testolactone is structurally related to testosterone and belongs to the first generation of aromatase inhibitors. It is a non-selective irreversible aromatase enzyme inhibitor that was one of the first steroids used in the clinical treatment of breast cancer. The use of testolactone in the treatment of breast cancer started in 1970, although its ability to inhibit aromatase was not discovered until 1975. Its use was primarily based on the inhibition of estrogen synthesis, which was applied in the treatment of estrogen-dependent breast cancers, in the treatment of disorders of sex steroid excess, familial male-limited precocious puberty, or in the treatment of patients with McCune–Albright syndrome, etc. The weak inhibitory activity of testolactone, and the moderate clinical response, prevented its widespread use, which ultimately resulted in withdrawal from the drug market in 2008. This review paper is dedicated to testolactone, its rise in the second half of the 20th century, and its fall in the first decade of the 21st century. Regardless of withdrawal from the market, for many years testolactone was a drug that improved the quality of life of patients facing one of the most serious diseases today, and for this reason, this paper describes medicinal application, synthesis, and modifications of testolactone.

Diastereodivergent Synthesis of A-Ring Lactones Derived from Cholesterol and Diosgenin: A Convenient Solution for an Old Problem – NMR and X-ray Characterization

“…1 Steroid lactones constitute a subfamily that includes several naturally occurring bioactive members, such as brassinolide ( 1 ), 2 bufalin ( 2 ), 3 and digitoxigenin ( 3 ) 4 (Figure 1 ). A wide variety of synthetic derivatives that include bioactive compounds such as dropinerone ( 4 ), 5 spironolactone ( 5 ), 6 and testolactone ( 6 ), 7 amongst many others, 8 has been also reported (Figure 1 ).…”

“…1 Steroid lactones constitute a subfamily that includes several naturally occurring bioactive members like Brassinolide (1), 2 Bufalin (2) 3 and Digitoxigenin (3). 4 A wide variety of synthetic derivatives that includes bioactive compounds like Dropinerone (4) 5 Spironolactone (5) 6 and Testolactone (6) 7 amongst many others, 8 has been also reported (Figure 1). As a part of our project on the synthesis of monomeric and dimeric heterocyclic steroids, we have become interested on the preparation of multigram amounts of A ring lactones 7a and 7b intended to serve as advanced synthetic intermediates in a wide variety of synthetic methodologies.…”

Biotransformation of Δ1-Progesterone Using Selected Entomopathogenic Filamentous Fungi and Prediction of Its Products’ Bioactivity

“…Hydroxylation predominantly occurs at the 6β and/or 11α positions; however, fungal cultures have also demonstrated the capability for hydroxylation at the 14α, 7α, 7β, 11β, 17α, 9α, 8β, 16α, 15α, 15β, 21, and 12β positions [ 20 , 21 , 22 ]. The Baeyer–Villiger oxidation of progesterone is possible through the biotransformation by some Aspergillus or Penicillium species [ 23 , 24 , 25 , 26 ].…”