Antiparasitic and Cytotoxic Activity of Bokkosin, A Novel Diterpene-Substituted Chromanyl Benzoquinone From Calliandra portoricensis

Abstract

Calliandra portoricensis is a medicinal plant growing freely in Nigeria. It is used traditionally to treat tuberculosis, as an anthelmintic and an abortifacient. Phytochemical fractionation and screening of its root extracts has yielded a novel (5-hydroxy-7-methoxy-4-oxo-1-chromanyl)-4-methoxy-p-benzoquinone (breverin)-substituted cassane diterpene, which was designated bokkosin. It was obtained from column chromatography of the ethyl acetate extract of the roots. The compound was characterized using IR, NMR (1D and 2D) and mass spectral data. Promising antiparasitic activity was observed against the kinetoplastid parasite Trypanosoma brucei brucei , as well as moderate activity against Trypanosoma congolense and Leishmania mexicana and low toxicity in mammalian cells, with the best in vitro EC 50 values against T. b. brucei (0.69 μg/mL against a standard laboratory strain, and its multi-drug resistant clone (0.33 μg/mL). The effect on T. b. brucei in culture was rapid and dose-dependent, leading to apparently irreversible growth arrest and cell death after an exposure of just 2 h at 2 × or 4 × EC 50 . The identification of bokkosin constitutes the first isolation of this class of compound from any natural source and establishes the compound as a potential trypanocide that, considering its novelty, should now be tested for activity against other microorganisms as well.

A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora

“…The compound showed potent activity against the kinetoplastid parasites, T. brucei (0.69 μg/mL), T. congolense (21.6 μg/mL), and L. mexicana (5.8 μg/mL). In addition, it exhibited very low prospects of cross-resistance to antitrypanosomal drugs, pentamidine and diminazene, and low toxicity to mammalian cell lines (Nvau et al, 2020 ). The ethyl acetate extracts of the leaves of Eucalyptus maculata also exhibited antitrypanosomal activity (12.3 ± 0.3 μg/mL, EC 50 ± SEM).…”

Cloning and Characterization of Trypanosoma congolense and T. vivax Nucleoside Transporters Reveal the Potential of P1-Type Carriers for the Discovery of Broad-Spectrum Nucleoside-Based Therapeutics against Animal African Trypanosomiasis

“…The use of the resazurin assay to investigate the toxicity of test compounds on mammalian cells and to quantify their selectivity for parasite cells has been reported previously [ 83 ]. Most of the assayed tubercidin analogs exhibited low toxicity against human embryonic kidney (HEK) cells ( Table 9 ), which translated into high selectivity to the parasites.…”

“…Promastigotes of L. mexicana Cas9 and derived cell lines were grown as described [ 29 ] with L. mexicana Cas9 maintained in 32 μg/mL hygromycin while the mutant SUPKO+NT strains were maintained with neomycin G418 at 50 μg/mL ([ 64 ]. Human embryonic kidney (HEK) cells were cultured and maintained as reported [ 83 ].…”

Plant Terpenoids as Hit Compounds against Trypanosomiasis

“…used in traditional medicine to treat tuberculosis, and helmintic diseases, showed a strong trypanocidal activity against the bloodstream forms of T. b. brucei , sensitive (IC 50 = 1.1. μM) and resistant to pentamidine (IC 50 = 0.5 μM). A highly favorable selectivity for the parasite strains was also observed, when compared with its cytotoxic effect on two mammalian cell lines (CC 50 = 269 μM; SI = 246, on U937; CC 50 = 230 μM; SI = 215, on RAW 246.7) [ 92 ].…”