Anti-Mycobacterial Activity and Inhibition of Polyketide Synthase 13-Thioesterase (Pks13-TE) by Aaptamine Alkaloids from the Sponge Aaptos aaptos: an in Vitro and in Silico Investigation

Background and objectives: Sponge Aaptos aaptosSchmidt is reported to have bioactive chemicals that can serve as medication substances. This research aimed to determine the antimycobacterial activity of alkaloid aaptamines from the sponge A. aaptos and study the molecular docking of the active compounds. Methods: The structural characterization of the isolated compounds was performed using spectroscopy techniques. Antimycobacterial activity was assessed against Mycobacterium smegmatis bacteria through the disc diffusion method. Molecular docking applied DOCK6 software, which incorporated grid values, flexible docking, and molecular mechanics generalized born surface area (MM-GBSA) methods, as well as the target protein polyketide synthase 13-thioesterase (Pks13-TE). Results:sponge A. aaptos produced three known alkaloids (1-3). Aaptamine (1) and isoaaptamine (2) were found to inhibit the bacteria M. smegmatis at the concentration of 50 g/disc with inhibition zone diameters of 9 and 13 mm, respectively. The compound demethyl(oxy)aaptamine (3) did not show any inhibition on the bacteria M. smegmatis at the concentration of 50 g/disc. Based on the results of grid score calculations using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method, the binding energy values (Hawkins_GBSA_Score) were as follows: aaptamine (1) showed a value : -26.766266, isoaptamine (2) : -27.401176, streptomycin sulfate : -31.428558, isoniazid : -21.507927, and native ligand : -23.506924. Aaptamine (1) and isoaaptamine (2) formed carbon-hydrogen bonded with the active site of the amino acid Asn: 1640 on the Pks13-TE enzyme. Conclusion: The alkaloids aaptamine (1) and isoaaptamine (2) from the sponge A. aaptos possess significant potential as therapeutic agents for tuberculosis.