Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11

Joint Authors

Fujita, Yukihisa
Akaho, Eiichi
Ali, Hamed I.
Yamada, Morio
Maeda, Mitsuko

Source

International Journal of Medicinal Chemistry

Issue

Vol. 2011, Issue 2011 (31 Dec. 2011), pp.1-11, 11 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2010-09-07

Country of Publication

Egypt

No. of Pages

11

Main Subjects

Chemistry
Pharmacology

Abstract EN

We investigated the 16α-hydroxylation of steroid molecules and regioselective binding mode in homology-modeled cytochrome P450-2C11 to correlate the biological study with the computational molecular modeling.

It revealed that there was a positive relationship between the observed inhibitory potencies and the binding free energies.

Docking of steroid molecules into this homology-modeled CYP2C11 indicated that 16α-hydroxylation is favored with steroidal molecules possessing the following components, (1) a bent A-B ring configuration (5β-reduced), (2) C-3 α-hydroxyl group, (3) C-17β-acetyl group, and (4) methyl group at both the C-18 and C-19.

These respective steroid components requirements were defined as the inhibitory contribution factor.

Overall studies of the male rat CYP2C11 metabolism revealed that the above-mentioned steroid components requirements were essential to induce an effective inhibition of [3H]progesterone 16α-hydroxylation.

As far as docking of homology-modeled CYP2C11 against investigated steroids is concerned, they are docked at the active site superimposed with flurbiprofen.

It was also found that the distance between heme iron and C16α-H was between 4 to 6 Å and that the related angle was in the range of 180±45∘.

American Psychological Association (APA)

Ali, Hamed I.& Yamada, Morio& Fujita, Yukihisa& Maeda, Mitsuko& Akaho, Eiichi. 2010. Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11. International Journal of Medicinal Chemistry،Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-508036

Modern Language Association (MLA)

Ali, Hamed I.…[et al.]. Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11. International Journal of Medicinal Chemistry No. 2011 (2011), pp.1-11.
https://search.emarefa.net/detail/BIM-508036

American Medical Association (AMA)

Ali, Hamed I.& Yamada, Morio& Fujita, Yukihisa& Maeda, Mitsuko& Akaho, Eiichi. Studies on 16α-Hydroxylation of Steroid Molecules and Regioselective Binding Mode in Homology-Modeled Cytochrome P450-2C11. International Journal of Medicinal Chemistry. 2010. Vol. 2011, no. 2011, pp.1-11.
https://search.emarefa.net/detail/BIM-508036

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-508036