Submitted to: Natural Product Communications
Publication Type: Peer reviewed journal
Publication Acceptance Date: 12/18/2008
Publication Date: 2/22/2009
Citation: Samoylenko, V., Khan, S.I., Jacob, M.R., Tekwani, B.L., Walker, L.A., Hufford, C.D., Muhammad, I. 2009. Bioactive (+)-Manzamine A and (+)-Hydroxymanzamine A Tertiary Bases and Salts from Acanthostrongylophora ingnes and Their Preparations. Natural Product Communications. 4(2):185-192. Interpretive Summary: Acanthostrongylophora ingens, a pacific marine sponge, yielded two tertiary bases (+)-8-hydroxymanzamine A (1) and (+)-manzamine A (2), and their salts (+)-8-hydroxy- manzamine A HCl (3) and (+)-manzamine A HCl (4), by alumina and silica gel chromatography, respectively, under same conditions. The antimalarial, antileishmanial and antimicrobial activity of the bases (1 and 2) and salts (3 and 4) were evaluated in this investigation.
Technical Abstract: The genus Acanthostrongylophora is famous for producing a wide array of manzamine alkaloids as natural hydrochloride salts. An examination of A. ingens has now yielded two tertiary bases, (+)-8-hydroxymanzamine A (1) and (+)-manzamine A (2), by chromatography over alumina using CHCl3-MeOH-NH3•H2O as solvent. In addition, (+)-8-hydroxymanzamine A hydrochloride (3) and (+)-manzamine A hydrochloride (4) were isolated by silica gel chromatography, under same conditions, from the same source. The structures of 1-4 were determined by 1D and 2D NMR spectra and Circular Dichroism experiments, and the spectral features of the bases 1 and 2 were found to be different from the salts 3 and 4. Compounds 3 and 4 were deprotonated by Al2O3 or strong base to afford 1 and 2, which were converted again to their respective salts 3 and 4. Both the compounds 1 and 3 showed equally potent in vitro antimalarial activity against chloroquine-sensitive (D6) and –resistant (W2) strains of P. falciparum (IC50= 19.5 and 22 ng/mL vs. 27 and 36.5 ng/mL, respectively), while 2 was >3-fold less potent than 4 (IC50= 20.8 and 25.8 ng/mL vs. 6.1 and 7.3 ng/mL, respectively). Compounds 1, 3 and 4 showed good antimicrobial activities against methicillin-resistant Staphylococcus aureus and Mycobacterium intracellulare and antileishmanial activity against Leishmania donovani promastigotes. In contrast, manzamine A base (2) showed relatively weaker antimicrobial, antileishmanial and cytotoxic activities towards cancer (HepG2: Human hepatocellular carcinoma or hepatoma), and non-cancer cells (VERO: Monkey kidney fibroblast; LLC-PK11: Pig kidney epithelial), compared to salt 4.