Study on the Anti- Activity of a Series of Marine-Derived 14-Membered Resorcylic Acid Lactone Derivatives.

With the emergence of drug-resistant strains, the treatment of tuberculosis (TB) is becoming more difficult and there is an urgent need to find new anti-TB drugs. , as a model organism of , can be used for the rapid and efficient screening of bioactive compounds. The 14-membered resorcylic acid lactones (RALs) have a wide range of bioactivities such as antibacterial, antifouling and antimalarial activity. In order to further study their bioactivities, we initially constructed a 14-membered RALs library, which contains 16 new derivatives. The anti- activity was evaluated in vitro. Derivatives , , and exhibited promising activity with MIC values of 80, 90, 80 and 80 μM, respectively. The preliminary structure-activity relationships showed that the presence of a chlorine atom at C-5 was a key factor to improve activity. Further studies showed that markedly inhibited the survival of and significantly reduced the dosage of positive drugs isoniazid and rifampicin when combined with them. These results suggest that is a bioactive compound capable of enhancing the potency of existing positive drugs, and its effective properties make it a very useful leads for future drug development in combating TB resistance.