RESUMEN
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.
Asunto(s)
Antibacterianos/farmacología , Fármacos Anti-VIH/farmacología , Antimaláricos/farmacología , Antineoplásicos/farmacología , VIH-1/efectos de los fármacos , Naftiridinas/química , Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Antimaláricos/síntesis química , Antimaláricos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Bacterias/efectos de los fármacos , Humanos , Leishmania donovani/efectos de los fármacos , Leucemia P388/tratamiento farmacológico , Malaria/tratamiento farmacológico , Ratones , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/efectos de los fármacos , Poríferos/química , Células Tumorales CultivadasRESUMEN
Two novel alkaloids, named manadomanzamines A (1) and B (2), were isolated from an Indonesian sponge Acanthostrongylophora sp. (Haplosclerida: Petrosiidae). Their structures were elucidated and shown to be a novel organic skeleton related to the manzamine type alkaloids. Their absolute configuration and conformation were determined by CD, NOESY, and molecular modeling analysis. The microbial community analysis for the sponge that produces these unprecedented alkaloids has also been completed. Manadomanzamines A (1) and B (2) exhibited strong activity against Mycobacterium tuberculosis (Mtb) with MIC values of 1.9 and 1.5 mug/mL, respectively. Manadomanzamines A and B also exhibit activities against human immunodeficiency virus (HIV-1) and AIDS opportunistic fungal infections.