Antimicrobial, antiparasitic and cytotoxic spermine alkaloids from Albizia schimperiana.
Albizia schimperiana Oliv. (Leguminosae) is a tree distributed in the highland of Kenya, where it is used as a traditional medicine for the treatment of bacterial and parasitic infections, notably pneumonia and malaria, respectively. Bioassay guided isolation of the CH2Cl2-MeOH 1:1/ MeOH-H20 9:1 (mixed) extract of A. schimperiana afforded the new bioactive macrocyclic spermine alkaloid, namely 5,14-dimethylbudmunchiamine L1 (1) and three known budmunchiamine analogs 2-4. The structures of the compounds 1-4 were determined by 1D and 2D NMR data, including COSY, HMQC, and HMBC experiments, and ESI-HRMS. Compounds 1 and 3 exhibited significant in vitro antimicrobial activity against a panel of microorganisms, including C neoformans, methicillin-resistant S. aureus, E. coli, M. intracellulare, and A. fumigatus. In Saddition, they demonstrated strong in vitro antimalarial activities against chloroquine-susceptible (D6) and -resistant (W2) strains of Plasmodium falciparum with IC50s ranging from 120-270 ng/mL. Compounds 1-4 were also evaluated for cytotoxic activity against selected human cancer cell lines and mammalian kidney fibroblasts (VERO cells). It was observed that hydroxyl substitution of the side chain of the budmunchiamines dramatically reduced the cytotoxicity and antimicrobial activity of the alkaloids 2 and 4 without decreasing antimalarial activity.
Samoylenko
Volodymyr
V
National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, Thad Cochran Research Center, The University of Mississippi, University, Mississippi 38677, USA.
Jacob
Melissa R
MR
Khan
Shabana I
SI
Zhao
Jianping
J
Tekwani
Babu L
BL
Midiwo
Jacob O
JO
Walker
Larry A
LA
Muhammad
Ilias
I
D031289:Albizzia / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D005658:Fungi / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010963:Plasmodium falciparum / Q000187:drug effects; D013096:Spermine / Q000737:chemistry / Q000494:pharmacology
D000470:Alkaloids; D000890:Anti-Infective Agents; D000972:Antineoplastic Agents, Phytogenic; D000977:Antiparasitic Agents; D013096:Spermine