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

John B Nvau; Samya Alenezi; Marzuq A Ungogo; Ibrahim A M Alfayez; Manal J Natto; Alexander I Gray; Valerie A Ferro; Dave G Watson; Harry P de Koning; John O Igoli

doi:10.3389/fchem.2020.574103

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

Front Chem. 2020 Nov 17:8:574103. doi: 10.3389/fchem.2020.574103. eCollection 2020.

Authors

Affiliations

¹ Department of Chemistry, Plateau State University, Bokkos, Nigeria.
² Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom.
³ College of Medical, Veterinary and Life Sciences, Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
⁴ Department of Veterinary Pharmacology and Toxicology, Ahmadu Bello University, Zaria, Nigeria.
⁵ Department of Chemistry, Phytochemistry Research Group, University of Agriculture, Makurdi, Nigeria.

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 EC₅₀ 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 × EC₅₀. 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.

Keywords: chroman-4-one; cytotocixicity; diterpene; leishmaniasis; trypanosomiasis.