New lipophilic phthalimido- and 3-phenoxybenzyl sulfonates: Inhibition of antigen 85C mycolyltransferase activity and cytotoxicity

Abstract

Four new sulfonates were prepared as potential inhibitors of antigen 85C, a mycolyl transferase involved in the biosynthesis of the mycobacterial cell wall being designed on the basis of the proposed catalytic mechanism and antigen 85C crystal structure. The inhibitors contained a sulfonate moiety, 3-phenoxybenzyl alcohol or N-(hydroxyethyl)phthalimide as trehalose mimetics, and an alkyl chain of different length mimicking either the mycolate (α-chain or the mycolic acid (β-branch. One compound displayed promising activity in a mycolyltransferase inhibition assay (compound 2b, IC₅₀ = 4.3 μM). The two compounds containing a phthalimide moiety (compounds 3a and 3b) showed significant and selective cytotoxicity against the breast cancer cell line MDA-MB231.

Keywords::

• Antigen 85C
• sulfonate inhibitors
• antituberculosis agents
• cytotoxicity
• anticancer agents, mycolyltransferase