New inhibitors of fungal 17β-hydroxysteroid dehydrogenase based on the [1,5]-benzodiazepine scaffold

Abstract

The synthesis and activity of a new series of non-steroidal inhibitors of 17β-hydroxysteroid dehydrogenase that are based on a 1,5-benzodiazepine scaffold are presented. Their inhibitory potential was screened against 17β-hydroxysteroid dehydrogenase from the fungus Cochliobolus lunatus (17β-HSDcl), a model enzyme of the short-chain dehydrogenase/reductase superfamily. Some of these compounds are potent inhibitors of 17β-HSDcl activity, with IC₅₀ values in the low micromolar range and represent promising lead compounds that should be further developed and investigated as inhibitors of human 17β-HSD isoforms, which are the enzymes associated with the development of many hormone-dependent and neuronal diseases.

Keywords::

• Benzodiazepines
• hydroxysteroid dehydrogenase
• inhibitors
• Cochliobolus lunatus
• anticancer agents
• docking
• 17β-HSDcl

Acknowledgements

This work was supported by the Ministry of Education, Science and Sport of the Republic of Slovenia. The authors wish to thank Dr Chris Berrie for critical reading of the manuscript.