Two New Antiprotozoal Diterpenes From the Roots of Acacia nilotica

John V Anyam; Priscilla E Daikwo; Marzuq A Ungogo; Nwakaego E Nweze; Ngozichukwuka P Igoli; Alexander I Gray; Harry P De Koning; John O Igoli

doi:10.3389/fchem.2021.624741

Two New Antiprotozoal Diterpenes From the Roots of Acacia nilotica

Front Chem. 2021 Apr 21:9:624741. doi: 10.3389/fchem.2021.624741. eCollection 2021.

Authors

John V Anyam¹, Priscilla E Daikwo¹, Marzuq A Ungogo^{2

3}, Nwakaego E Nweze⁴, Ngozichukwuka P Igoli⁵, Alexander I Gray⁶, Harry P De Koning², John O Igoli¹

Affiliations

¹ Phytochemistry Research Group, Department of Chemistry, University of Agriculture, Makurdi, Nigeria.
² Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
³ Department of Veterinary Pharmacology and Toxicology, Ahmadu Bello University, Zaria, Nigeria.
⁴ Department of Veterinary Medicine, Faculty of Veterinary Medicine, University of Nigeria, Nsukka, Nigeria.
⁵ Centre for Food Technology and Research, Benue State University, Makurdi, Nigeria.
⁶ Strathclyde Institute of Pharmacy and Biomedical Science, University of Strathclyde, Glasgow, United Kingdom.

Abstract

The powdered roots of the medicinal plant Acacia nilotica were extracted with hexane and ethyl acetate, and the extracts were subjected to column chromatography for the isolation of potentially bioactive compounds and their screening against kinetoplastid pathogens. NMR and HREI mass spectrometric analyses identified two new diterpenes, characterized as 16, 19-dihydroxycassa-12-en-15-one (Sandynone, 1) and (5S, 7R, 8R, 9R, 10S, 13Z, 17S)-7,8:7,17:16,17-triepoxy-7,8-seco-cassa-13-ene (niloticane B, 2). The previously reported (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-diene-7,17-diol (3), (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol-17-al (4), and (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol (5) a, mixture of stigmasterol (6a) and sitosterol (6b), and lupeol (7) were also isolated. Several column fractions displayed significant activity against a panel of Trypanosoma and Leishmania spp., and from the most active fraction, compound 4 was isolated with high purity. The compound displayed high activity, particularly against T. brucei, T. evansi, and L. mexicana (0.88-11.7 µM) but only a modest effect against human embryonic kidney cells and no cross-resistance with the commonly used melaminophenyl arsenical and diamidine classes of trypanocides. The effect of compound 4 against L. mexicana promastigotes was irreversible after a 5-h exposure, leading to the sterilization of the culture between 24 and 48 h.

Keywords: Acacia nilotica; Leishmania; Nigeria; diterpenes; seco-oxocassanes; spectroscopy; trypanosomiasis.