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Synthesis of steroidal inhibitors for Mycobacterium tuberculosis
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...
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Published in: | The Journal of steroid biochemistry and molecular biology 2024-05, Vol.239, p.106479, Article 106479 |
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Main Authors: | , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | 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.
•Synthesis and evaluation of 28 cholesterol derivates as Mtb inhibitors.•Evaluation of MIC with virulent Mtb.•Evaluation of in vitro binding to CYP125A1 as potential target. |
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ISSN: | 0960-0760 1879-1220 1879-1220 |
DOI: | 10.1016/j.jsbmb.2024.106479 |