Work

New Structure Activity Relationship Insight into the Role of the C‐3 Extension on Rifamycin Antimycobacterial Activity

Year: 2025

Type: article

Abstract: Herein, the antimycobacterial screening of a series of rifamycin analogues, modified at their C-3 extension, is reported. Overall, these compounds display potent activity against a wild-type Mtb strain assayed in three different growth media. Several promising C-3 extensions are identified through this screen, with compounds featuring rigid tertiary alicyclic hydrazones displaying superior activity to amino compounds. In addition, a general correlative trend between logP and biological activity is observed. This study adds to the growing literature surrounding structure activity relationship pertaining the important C-3 extension of rifamycin, which in addition to a poorly understood role in target engagement, has utility for modulating physicochemical properties, a key condition in antimycobacterial drug discovery.

Source: ChemMedChem

DOI: 10.1002/cmdc.202500673

Authors: Clinton G. L. Veale, Ewelina Smolarz, Aleksandra Leśniewska, Krystian Pyta, Piotr Przybylski

Institutions: University of Cape Town, Adam Mickiewicz University in Poznań

Language: English

Topic: Microbial Natural Products and Biosynthesis

Subfield: Pharmacology

Field: Medicine

Domain: Health Sciences

Open Access status: hybrid

Estimated APC paid: $4,150

Funders: National Research Foundation, University of Cape Town