Synthesis of steroidal inhibitors for Mycobacterium tuberculosis
Date
2024
Authors
Churchman, L.R.
Beckett, J.R.
Tan, L.
Woods, K.
Doherty, D.Z.
Ghith, A.
Bernhardt, P.V.
Bell, S.G.
West, N.P.
De Voss, J.J.
Editors
Advisors
Journal Title
Journal ISSN
Volume Title
Type:
Journal article
Citation
Journal of Steroid Biochemistry and Molecular Biology, 2024; 239:106479-1-106479-16
Statement of Responsibility
Luke R. Churchman, James R. Beckett, Lendl Tan, Kyra Woods, Daniel Z. Doherty, Amna Ghith, Paul V. Bernhardt, Stephen G. Bell, Nicholas P. West, James J. De Voss
Conference Name
Abstract
Oxidised derivatives of cholesterol have been shown to inhibit the growth of Mycobacterium tuberculosis (Mtb). The bacteriostatic activity of these compounds has been attributed to their inhibition of CYP125A1 and CYP142A1, two metabolically critical cytochromes P450 that initiate degradation of the sterol side chain. Here, we synthesise and characterise an extensive library of 28 cholesterol derivatives to develop a structure-activity relationship for this class of inhibitors. The candidate compounds were evaluated for MIC with virulent Mtb and in binding studies with CYP125A1 and CYP142A1 from Mtb.
School/Discipline
Dissertation Note
Provenance
Description
Available online 10 February 2024
Access Status
Rights
© 2024 Published by Elsevier Ltd.