New antimycobacterial sulfonamide-based ureas

Abstract

Certain antimicrobial properties of sulfonamide-type compounds have been described many times.1 We focused our attention on a drug containing the aforementioned sulfonamide group, which originally had no antimicrobial properties. We began modifying this drug and achieved remarkable results.We present a comprehensive series of new compounds with highly promising antimycobacterial activity derived from the original antidiabetic drug carbutamide. Through logically applied structural modifications of the carbutamide molecule and subsequent detailed analysis of structurally active relationships (SAR), we succeeded in obtaining compounds with a minimum inhibitory concentration value of lower than 1 µM against drug susceptible M. tuberculosis H37Rv.Preliminary evaluation results indicate that some of these compounds will have optimal water solubility, and due to the applied isosteric substitution modification of the sulfonamide group, we also expect promising activity against mycobacterial strains with different resistance profiles. An extension of the spectrum of efficacy towards non-tuberculous mycobacteria cannot be ruled out as well. Further tests are ongoing.