Voulkensin C–E, new 11-oxocassane-type diterpenoids and a steroid glycoside from Caesalpinia volkensii stem bark and their antiplasmodial activities Charles O. Ochieng a,⇑ , Lawrence A. O. Manguro a , Philip O. Owuor a , Hosea Akala b a Department of Chemistry, Maseno University, Private Bag, 40105 Maseno, Kenya b United State Army Medical Research Unit, Water Reed Project, P.O Box 54, Kisumu, Kenya article info Article history: Received 12 November 2012 Revised 25 February 2013 Accepted 4 March 2013 Available online xxxx Keywords: Caesalpinia volkensii 11-Oxocassane-type diterpenoids 3-O-[b-Glucopyranosyl(1?2)-O-b- xylopyranosyl]-stigmasterol Antiplasmodial abstract A bioassay guided isolation of potential antimalarial molecules from the stem bark of Caesalpinia volkensii Harms (Fabaceae) achieved three new 11-oxocassane-type diterpenoids named voulkensin C (1), D (2) and E (3) together with one steroid glycoside named 3-O-[b-glucopyranosyl(1?2)-O-b-xylopyranosyl]- stigmasterol (4) and seven other known compounds including stigmasterol (5), b-sitosterol (6), oleanolic acid (7), 3-b-acetoxyolean-12-en-28-methyl ester (8), voucap-5-ol (9), caesadekarin C (10), deoxycaesal- dekarin C (11). The structures of the new compounds were determined on the basis of extensive spectro- scopic data (IR, MS, 1 H and 13 C NMR and 2D NMR) analyses. The polar extracts revealed moderate to good antiplasmodial activities against chloquine-sensitive (D6) and -resistant strains (W2) of Plasmodium falciparum. Whereas the pure isolates exhibited limited to moderate antiplasmodial activities with com- pound 4 showing the highest antiplasmodial activities (IC 50 values of 4.44 ± 0.88 and 2.74 ± 1.10 lM against D6 and W2 strains, respectively). These results suggest a possible contribution of phytochemicals from C. volkensii stem bark towards inhibition of plasmodial parasites’ growth hence potential antimalarial. Ó 2013 Elsevier Ltd. All rights reserved. Malaria is still one of the major health problems in many trop- ical countries, despite efforts to eradicate the mosquito’s vector through the use of insecticides and supply of several antimalarial drugs. The resurgence of drug-resistant Plasmodium falciparum since 1960 has made the treatment of malaria increasingly prob- lematic, 1 and the battle against malaria is far from being won. Although malaria is in principle a preventable and curable disease, in practice the majority of the population in the poor developing tropical countries, are still at risk. This is due to high cost of mod- ern treatment causing a need for alternative cheap and accessible chemotherapeutics. 2 One possible source of such treatment lies in the traditional herbal remedies used by the ethnomedicinal practitioners in the developing world. From the historical discov- ery of quinine from the Cinchona tree and the recent discovery of artemisinin from Artemisia annua L. (Asteraceae), there is anticipa- tion that new lead compounds, with interesting structural may emerge from other tropical plants sources. Caesalpinia volkensii Harms. (Fabaceae) is a popular traditional medicinal plant sparsely distributed within the tropical highlands regions of eastern Africa. 3 In Kenya, herbalist prescribe concoction of the leaves, stem bark and root bark to manage malaria fever, sometimes alone, but more often mixed with other plants. 2,3 The leaf, root bark or stem bark and powered fruits decoction are consumed to fight pain during pregnancy. 3 Unspecified plant parts are used in Kenya to treat retinosblastoma. 3 In vitro tests of leaf extracts of C. volkensii showed antiplasmodial activity against chlo- roquine-resistant strains of Plasmodium falciparum. 2 Previous phy- tochemical study reported furanoditerpenoids from the root bark of C. volkensii with moderate antiplasmodial and good antinocicep- tive activities. 4 In general, plants of the sub family Caesalpiniaceae contain cassane furanodeterpene, 5 biflavonoids, 6 homoisoflav- ones, 7 triterpenes and phenylpropanoids, 8 some of which display antiviral, antimalarial, antibacterial, anti-inflammatory and antiox- idant activities. 5,8,9 As a part of continued exploration of this medicinal plant resources from Kenya, we observed that medium polar and polar extracts (CH 2 Cl 2 , EtOAc and n-butanol extracts) of the stem bark of C. volkensii possessed significant antimalarial activity in vitro. Separation and purification of the extracts led to the isolation of three new cassane diterpenes [voulkensin C, (1), voulkensin D, (2), and voulkensin E, (3)] and one new steroidal gly- coside [3-O-[b-glucopyranosyl(1?2)-O-b-xylopyranosyl]-stigmas- terol (4)] together with two common steroids [stigmasterol (5) and b-sitosterol (6)], 10–12 two triterpenes [oleanolic acid (7) and 3-b-acetoxyolean-12-en-28-methyl ester (8)], 12,13 and cassane furanoditerpene [(voucapan-5-ol (9), caesaldekarin C (10) and 0960-894X/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bmcl.2013.03.007 ⇑ Corresponding author. Tel.: +254 726915429; fax: +254 57351221/351153. E-mail address: otieno.charles9@gmail.com (C.O. Ochieng). Bioorganic & Medicinal Chemistry Letters xxx (2013) xxx–xxx Contents lists available at SciVerse ScienceDirect Bioorganic & Medicinal Chemistry Letters journal homepage: www.elsevier.com/locate/bmcl Please cite this article in press as: Ochieng, C. O.; et al. Bioorg. Med. Chem. Lett. (2013), http://dx.doi.org/10.1016/j.bmcl.2013.03.007