A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase.

A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Research Abstract Details 

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A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Abstract Text:

Urmi Dhagat,Vincenzo Carbone,Roland P-T Chung,Toshihiro Matsunaga,Satoshi Endo,Akira Hara,Ossama El-Kabbani,Urmi Dhagat,Vincenzo Carbone,Roland P-T Chung,Toshihiro Matsunaga,Satoshi Endo,Akira Hara,Ossama El-Kabbani,

20alpha-hydroxysteroid dehydrogenase (AKR1C1) plays a key role in the metabolism of progesterone and other steroid hormones, thereby regulating their action at the pre-receptor level. AKR1C1 is implicated in neurological and psychiatric conditions such as catamenial epilepsy and depressive disorders. Increased activity of AKR1C1 is associated with termination of pregnancy and the development of breast cancer, endometriosis and endometrial cancer. Inhibition of the undesired activity of AKR1C1 will help reduce risks of premature birth, neurological disorders and the development of cancer. In order to identify potential leads for new inhibitors of AKR1C1 we adopted a virtual screening-based approach using the automated DOCK program. Approximately 250,000 compounds from the NCI database were screened for potential ligands based on their chemical complementarity and steric fit within the active site of AKR1C1. Kinetic analysis revealed 3,5-diiodosalicylic acid, an analogue of salicylic acid, as a potent competitive inhibitor with respect to the substrate 5beta-pregnane-3alpha,20alpha-diol with a K(i) of 9 nM. Aspirin, which is a well known salicylic acid-based drug, was also found to inhibit AKR1C1 activity. This is the first report to show aspirin (IC(50)=21 microM) and its metabolite salicylic acid (IC(50)=7.8 microM) as inhibitors of AKR1C1.

A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Publishing Authors By Initials

U Dhagat,V Carbone,RP Chung,T Matsunaga,S Endo,A Hara,O El-Kabbani,U Dhagat,V Carbone,RP Chung,T Matsunaga,S Endo,A Hara,O El-Kabbani,

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A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Medicinal chemistry (Sh?ariqah, United Arab Emirat

VOLUME: 3

Page Numbers: 546-50

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ISSN: 1573-4064

DAY: 29

MONTH: Nov

YEAR: 2007

A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase. Information

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LANGUAGE: eng

NlmUniqueID: 101240303

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Grant and Affiliation Information for A salicylic acid-based analogue discovered from virtual screening as a potent inhibitor of human 20alpha-hydroxysteroid dehydrogenase.

AFFILIATION: Department of Medicinal Chemistry, Victorian College of Pharmacy, Monash University (Parkville Campus), Parkville, Victoria 3052, Australia.

Country: Netherlands

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MEDLINETA: Med Chem

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