New polyisoprenylated polycyclic phloroglucines from Clusia gundlachii

Authors: ZHANG, JIN - University Of Mississippi; ZHAO, JIANPING - University Of Mississippi; SAMOYLENKO, VOLODYMYR - University Of Mississippi; JAIN, SURENDRA - University Of Mississippi; TEKWANI, BABU - University Of Mississippi; MUHAMMAD, ILIAS - University Of Mississippi

Submitted to: Natural Product Communications
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/5/2018
Publication Date: 3/13/2018
Citation: Zhang, J., Zhao, J., Samoylenko, V., Jain, S., Tekwani, B.L., Muhammad, I. 2018. New polyisoprenylated polycyclic phloroglucines from Clusia gundlachii. Natural Product Communications. 13(3):361-365.

Interpretive Summary: Clusia gundlachii, commonly known as Grundlach’s attorney, is a perennial shrub, tree or vine of the genus Clusia. In this investigation, we aimed to discover novel bioactive compounds to treat parasitic diseases, such as malaria and leishmania. We have isolated and elucidated the structures of five new polycyclic phloroglucine derivatives from the fruits of C. gundlachii. The antimalarial and antileishmanial activities of compounds 1-5 were evaluated, with antileishmanial activity for 1 and 3 against L. donovani intracellular macrophage amastigotes in THP1 cultures. They showed no cytotoxicity against transformed THP 1 cells. This activity was comparable to those observed for the reference drug pentamidine. Furthermore, these compounds showed weak antimalarial activity. This appears to be the first report of polycyclic phloroglucines 1-5 from a natural source, and compounds 1 and 3 are potential lead candidates for further development of antileishmanial drugs.

Technical Abstract: A bioassay-guided fractionation yielded five new polycyclic phloroglucines derivatives, namely, gundlachiione A (1), gundlachiione B (2), gundlachiione C (3), gundlachiione D (4) and gundlachiione E (5) from the fruits of Clusia gundlachii, collected in Puerto Rico, USA. Their structures were determined by full spectroscopic data, including 2D NMR COSY, HMQC, HMBC, and NOESY experiments, and HRESIMS. Compounds 1 and 3 demonstrated activities against Leishmania donovani intracellular macrophage amastigotes in THP1 cultures, comparable to those observed for the standard drug pentamidine (IC50 and IC90 values 0.84 and 6.13 µg/mL, 2.32 and 3.01 µg/mL, 0.77 and 2.99 µg/mL, respectively). Both compounds, 1 and 3, also showed weak activities against L. donovani promastogotes and absence of cytotoxicity against transformed THP 1 cells.