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

TITLE=Two New Antiprotozoal Diterpenes From the Roots of Acacia nilotica

JOURNAL=Frontiers in Chemistry

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2021.624741

DOI=10.3389/fchem.2021.624741

ISSN=2296-2646

ABSTRACT=<p>The powdered roots of the medicinal plant <italic>Acacia nilotica</italic> 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, <bold>1</bold>) and (5S, 7R, 8R, 9R, 10S, 13Z, 17S)-7,8:7,17:16,17-triepoxy-7,8-seco-cassa-13-ene (niloticane B, <bold>2</bold>). The previously reported (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-diene-7,17-diol (<bold>3</bold>), (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol-17-al (<bold>4</bold>), and (5S,7R,8R,9R,10S) -(-)-7,8-seco-7, 8-oxacassa-13,15-dien-7-ol (<bold>5</bold>) a, mixture of stigmasterol (<bold>6a</bold>) and sitosterol (<bold>6b</bold>), and lupeol (<bold>7</bold>) were also isolated. Several column fractions displayed significant activity against a panel of <italic>Trypanosoma</italic> and <italic>Leishmania</italic> spp., and from the most active fraction, compound <bold>4</bold> was isolated with high purity. The compound displayed high activity, particularly against <italic>T. brucei</italic>, <italic>T. evansi</italic>, and <italic>L. mexicana</italic> (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 <bold>4</bold> against <italic>L. mexicana</italic> promastigotes was irreversible after a 5-h exposure, leading to the sterilization of the culture between 24 and 48 h.</p>