In silico study of bioactive compounds derived from Indonesian marine invertebrates as novel antituberculosis agent

Absztrakt

Background/aim: Tuberculosis has still become the most deadly disease globally. The problem of finding an effective therapeutic is one of the obstacles in the treatment of patients. Marine invertebrates were a treasure since they produced many active compounds. Following up on this issue, screening active compounds is very important. This study will explain the result of anti-tuberculosis screening of compounds derived from marine invertebrates using in silico and confirmed to the in vitro-data.Materials and methods: Three-dimensional (3D) structures of pantothenate kinase (MtPanK type 1, PDB ID: 4BFT), Mycobacterium tuberculosis InhA (MtInhA, PDB ID: 2X23), protein kinase B (PDB ID: 5U94), and β-ketoacyl acyl carrier protein synthase I (MtKasA, PDB ID: 2WGE) were used as protein targets. Confirmation of in-vitro studies was done to the potential marine sponges as the targeted compounds. Results: The molecular docking analysis showed that the lowest docking scores were: 19-hydroxypsammaplysin Q against MtPank type 1 (-129.956), 19-hydroxypsammaplysin S towards MtInhA (-131.310), psammaplysin L against protein kinase B (-121.875), and psammaplysin K dimethoxy acetal against MtKasA (-127.916), while no reported in-vitro data supported yet. However several compounds such as molamide C and manzamine group are also on the top ten docking scores and the previous in vitro evaluation showed potential antituberculosis compounds. The preliminary in-vitro study of a compound derived from the genus Pseudoceractina that related to psammaplysins through bromotyrosine pathway was subereamide A. It showed activity against Mycobacterium smegmatis with MIC values comparable to the rifampicin. This data was also supported by the molecular docking score of subereamide A which was insignificant to the psammaplysin groups. Conclusion: This study proved that psammaplysin group, subereamide A, mollamide C and achantomanzamine have potential as anti-TB compounds. A further analysis of compounds derived from the Verongiidae family will be done to confirm the detailed in silico data.