Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity.

As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of new semisynthetic products was evaluated for biological activity against HIV-1, Mtb, AIDS-OI, tropical parasitic diseases, and cancer. Compound 4 showed potent activity against HIV-1 (EC(50) 0.47microg/mL), compound 19 proved to possess remarkable activity against Mycobacterium intracellulare with an IC(50) and MIC value of 0.15 and 0.31microg/mL, while compounds 4 and 17 possessed anti-leishmanial activity with IC(50) values of 0.1 and 0.4microg/mL, respectively. Compounds 16 and 17 showed antimalarial activity with EC(50) values of 230 and 240ng/mL, respectively, and compound 14 exhibited an EC(50) of 0.05microM against the Leukemia cell line K-562.