1. Synthesis of steroidal inhibitors for Mycobacterium tuberculosis.
- Author
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Churchman LR, Beckett JR, Tan L, Woods K, Doherty DZ, Ghith A, Bernhardt PV, Bell SG, West NP, and De Voss JJ
- Subjects
- Cytochrome P-450 Enzyme System metabolism, Cholesterol metabolism, Structure-Activity Relationship, Mycobacterium tuberculosis
- 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., (Copyright © 2024. Published by Elsevier Ltd.)
- Published
- 2024
- Full Text
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