Background: New drugs and strategies to treat tuberculosis (TB) are urgently needed.
In this context, thiourea derivatives have a wide range of biological activities, including anti-TB.
This fact can be illustrated with the structure of isoxyl, an old anti-TB drug, which has a thiourea
as a pharmacophore group.
Objective: The aim of this study is to describe the synthesis and the antimycobacterial activity of
fifty-nine benzoylthioureas derivatives.
Methods: Benzoylthiourea derivatives have been synthesized and evaluated for their activity
against Mycobacterium tuberculosis using the MABA assay. After that, a structure-activity relationship
study of this series of compounds has been performed.
Results and Discussion: Nineteen compounds exhibited antimycobacterial activity between 423.1
and 9.6 μM. In general, we observed that the presence of bromine, chlorine and t-Bu group at the
para-position in benzene ring plays an important role in the antitubercular activity of Series A.
These substituents were fixed at this position in benzene ring and other groups such as Cl, Br, NO2
and OMe were introduced in the benzoyl ring, leading to the derivatives of Series B. In general,
Series B was less cytotoxic than Series A, which indicates that the presence of a substituent at
benzoyl ring contributes to an improvement in both antimycobacterial activity and toxicity profiles.
Conclusion: Compound 4c could be considered a good prototype to be submitted to further structural
modifications in the search for new anti-TB drugs, since it is 1.8 times more active than the
first line anti-TB drug ethambutol and 0.65 times less active than isoxyl.