Bioactive (+)-manzamine A and (+)-8-hydroxymanzamine A tertiary bases and salts from Acanthostrongylophora ingens and their preparations.
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 under the same conditions from the same source by silica gel chromatography. The structures of 1-4 were determined from 1D- and 2D-NMR spectra and by circular dichroism experiments, and the spectral features of the bases 1 and 2 were found to be different from those of the salts 3 and 4. Compounds 3 and 4 were deprotonated by both A12O3 and 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 22.0 ng/mL vs. 27.0 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 with salt 4.
Samoylenko
Volodymyr
V
National Center for Natural Products Research, School of Pharmacy, University of Mississippi, 38677, USA.
Khan
Shabana I
SI
Jacoba
Melissa R
MR
Tekwani
Babu L
BL
Walker
Larry A
LA
Hufford
Charles D
CD
Muhammad
Ilias
I
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000737:chemistry*; D002243:Carbolines / Q000737:chemistry*; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D000981:Antiprotozoal Agents; D002227:Carbazoles; D002243:Carbolines; C078290:manzamine A; C086783:8-hydroxymanzamine A