| Abstract |
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Tuberculosis caused by Mycobacterium tuberculosis is an infectious disease spread world wide. This bacterium have already been resistant to commercially available antibiotics. Thus, discovery of new antibiotics to counter measure this disease is an urgent effort. Our previous study found that several mangrove and sponge produce bioactive substances against M. tuberculosis. Preliminary purification process resulted partial purified substances with MIC of 21,53 and 23,75 µg/mL. Based on the our previous results, the main objectives of this research are (1) to purify anti-TB substance from active Indonesian mangrove and sponge (2) to elucidate the chemical structure of purified anti-TB substances (3) to screen anti-TB activity from new resources of mangrove, sponge and microorganism, (4) to develop synthetic compounds xanthones for anti-TB activity, and (5) to synthesize and screen anti-TB activity of curcumin analogs and multicompounent reaction (MCR) products, (6) to evaluate in vitro activity of anti-TB substances.
Indonesia is a well known country with mega biodiversity either in terrestrial or marine ecosystems. Several marine bioresources such as sponge, mangrove and marine microorganism show promising antibacterial activity. Indonesian medical plants easily found in house garden, shows anti-TB activity in our previous research. In this research we will screen the extracts for anti-TB activity from wider biodiversity resources of sponge, mangrove and marine microorganism, purify active compound and elucidate the chemical structure. Besides the effort to find new resources for anti-TB substances, we will purified the anti-TB substances from anti-TB-producing Mangrove and sponge especially BR12D and WO4. Purification will be conducted by bioactivity guided isolation by mean of column chromatography, TLC and HPLC. The chemical structure elucidation will be conducted by means of NMR, IR, GC-MS and LC-MS.
Previous work has shown that several xanthones compounds are active against Mycobacterium tuberculosis. It has been proven as well that the existence of hydroxy groups could increase the anti TB activity of the compounds. Nonetheless, the xanthone compounds were obtained through isolation from an Indonesian fruit, Garcinia mangostana in a very low yield (0.03 %) which prevents their further application as anti TB drugs. Based on this phenomenon, here we propose an efficient method for developing xanthone compounds as anti TB drugs on the basis of QSAR study and synthetic approaches. The QSAR study will be performed through PM3 method which so far being highly accurate even though this is rather slow. The synthesized compounds will be characterized by means of IR, NMR, GC-MS and LC-MS. Besides xanthones, curcumin is an Indonesian lead compound which have already been succesfully synthesized . Curcumin is isolated and purified from an Indonesian plant, Curcuma sp. Three curcumin analogs, PGV-6, HGV-6 and GVT-6, show promising activity against M. tuberculosis. Therefore, in this research we would like to develop these analogs to discover new anti-TB drugs.
Kewords: QSAR, synthesis, polyhydroxyxanthone, curcumin, isolation, and anti tuberculosis, natural product |
