ANTITUBERCULOSIS LANOSTANE TRITERPENOID AND METHOD OF MAKING THE COMPOUNDS

摘要

A new lanostane triterpenoid (24E)-3β-acetoxy-15α-propionyloxylanosta-7,9( 11 ),24-trien-26-oic acid (GA003), is synthesized by acylation reaction of a naturally occurring fungal metabolite, (24E)-3β-acetoxy-15α-hydroxylanosta-7,9( 11 ),24-trien-26-oic acid (ganoderic acid T-O). GA003 is identified as the most potent antimycobacterial against Mycobacterium tuberculosis H37Ra (MIC 0.0977 μg/ml) through a series of structural modifications (semi-synthesis) of a lead natural product, (24E)-3β,15α diacetoxylanosta-7,9(1 1),24-trien-26-oic acid. GA003 exhibits potent growth inhibitory activity against Mycobacterium tuberculosis strains H37Rv (virulent strain), THX-0001 (pre-XDR strain), THX-0002 (XDR strain), and THX-0003 (XDR strain), with MIC values of 0.3125, 0.156, 0.625, and 1.25 μg/ml, respectively, while showing very weak cytotoxicity to Vero cells (African green monkey kidney fibroblasts). Therefore, GA003 and pharmaceutical compositions containing GA003 may be useful for the treatment of tuberculosis.