PHYTOCHEMISTRY Phytochemistry 68 (2007) 663–667 www.elsevier.com/locate/phytochem Acridone and furoquinoline alkaloids from Teclea gerrardii (Rutaceae: Toddalioideae) of southern Africa Alain F. Kamdem Waffo a,b, Philip H. Coombes a,*, Neil R. Crouch a,c, Dulcie A. Mulholland a,d, Sawsan M.M. El Amin a, Peter J. Smith e a School of Chemistry, University of KwaZulu-Natal, Howard College Campus, 4041, Durban, South Africa Department of Chemistry, Faculty of Science, University of Douala, P.O. Box 24157 Douala, Cameroon c Ethnobotany Unit, South African National Biodiversity Institute, P.O. Box 52099, Berea Road 4007, South Africa d School of Biomedical and Molecular Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom Pharmacology Division, Department of Medicine, University of Cape Town, K-45 OMB GSH, Observatory 7295, South Africa b e Received 12 September 2006; received in revised form 9 October 2006 Available online 15 December 2006 This paper is dedicated to the memory of the late Ms Sawsan Mekki El Amin. Abstract The combined hexane/CH2Cl2 extract of the stem bark of Teclea gerrardii (Rutaceae: Toddalioideae) has yielded two acridone alkaloids, 3-hydroxy-1-methoxy-N-methylacridone (tegerrardin A) (1) and 3-hydroxy-N-methyl-1-(c,c-dimethylallyloxy)acridone (tegerrardin B) (2), three known acridones (3–5), two known furoquinolines (6,7), and the acridone precursor tecleanone (8). Arborinine (3) and evoxine (6) displayed moderate antiplasmodial activity against the CQS D10 strain of Plasmodium falciparum, with IC50 values of 12.3 and 24.5 lM, respectively. Ó 2006 Elsevier Ltd. All rights reserved. Keywords: Teclea gerrardii; Rutaceae; Stem bark; Acridone alkaloids; Furoquinoline alkaloids; 3-Hydroxy-1-methoxy-N-methylacridone (tegerrardin A); 3-Hydroxy-N-methyl-1-(c,c-dimethylallyloxy)acridone (tegerrardin B); Arborinine; Evoxanthine; 1,3-Dimethoxy-N-methylacridone; Evoxine; 7-(c,c-Dimethylallyloxy)-c-fagarine; Tecleanone; Plasmodium falciparum; Antiplasmodial activity 1. Introduction Teclea gerrardii I.Verd., the Flaky cherry-orange, is an aromatic shrub or tree (to 15 m) occurring in riverine thicket and dry forest along the eastern seaboard of southern Africa, in which region it is known from South Africa, Swaziland and southern Mozambique. As a genus of about 22 species, Teclea Del. is restricted to Africa and the Mascarenes (Victor, 2000) and has been assigned to the subtribe Amyridinae in the subfamily Toddalioideae of the Rutaceae (Engler, 1931). Continentally, Teclea is the * Corresponding author. E-mail address: Coombesp@ukzn.ac.za (P.H. Coombes). 0031-9422/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2006.10.011 most widely distributed of the African Toddalioideae (Verdoorn, 1926) though with most taxa localised in the tropics, only three species are known from the Flora of Southern Africa (FSA) region. T. gerrardii is known to the Zulu as umboza or umozane and is employed in traditional medicine; bark decoctions are taken for chest complaints (Hutchings et al., 1996). Whilst South African material of T. natalensis has previously been the subject of phytochemical study (Tarus et al., 2005), T. gerrardii has not. Accordingly, the current investigation sought chemically to profile this medicinal plant and to interpret findings in view of earlier chemotaxonomic assessments of African Toddalioideae (Waterman, 1973; Waterman et al., 1978; Dagne et al., 1988). 664 A.F. Kamdem Waffo et al. / Phytochemistry 68 (2007) 663–667 2. Results and discussion In continuation of our studies on southern African rutaceaeus taxa (Naidoo et al., 2005; Tarus et al., 2005, 2006; Mbala, 2006), we report the isolation of two novel acridone alkaloids, together with three known acridones, two known furoquinolines, and an aminobenzophenone, from the combined hexane/CH2Cl2 extract of the stem bark of T. gerrardii. An HREIMS of tegerrardin A 1 showed an [M]+ peak at m/z 255.0896, corresponding to the molecular formula C15H13NO3. Inspection of the IR, 1H and 13C NMR spectra of 1 showed it to possess a carbonyl carbon (dC 180.6(C); 1639 cm 1, C@O stretch), an aromatic methoxy group (dH 3.86 s, 3H; dC 55.5 (CH3)), an N-methyl group (dH 3.73 s, 3H; dC 34.0 (CH3)), and six aromatic proton signals. A correlation in the HMBC spectrum between the C-9 carbonyl resonance and a 1H doublet signal at dH 8.39 (J = 8.1 Hz) established this as H-8, with correlations in the COSY spectrum then permitting the assignment of 1H multiplet resonances at dH 7.24 and 7.65, and a 1H doublet signal at dH 7.43 (J = 8.6 Hz), to H-7, H-6 and H-5, respectively, of the unsubstituted A ring of an acridone alkaloid. These assignments were confirmed by a correlation in the NOESY spectrum between the latter signal and that of the N-methyl group, which also displayed a further correlation to the more upfield signal of a pair of mcoupled aromatic protons (dH 6.23, 6.24, each d, J = 2.2 Hz), which was assigned to H-4. A further correlation in the NOESY spectrum between the methoxy group resonance and that at dH 6.24, assigned to H-2, but not to that of H-4, placed this at C-1, and the remaining O and H atoms are accounted for by placing a hydroxy group at C-3. As 3-hydroxy-1-methoxy-N-methylacridone, tegerrardin A 1 is reported here for the first time from a natural source, although it has previously been synthesized (Hlubucek et al., 1970; Su and Chou, 1994), while the closely related 1-hydroxy-3-methoxy-N-methylacridone and 1,3dimethoxy-N-methylacridone are widespread in the Rutaceae (Dictionary of Natural Products, 2006). The 1H and 13C NMR spectra of tegerrardin B 2 were similar to those of 1 (dC 180.8 (C), C-9; dH 8.39, d, J = 8.1 Hz, H-8; dH 7.27, m, H-7; dH 7.71, m, H-6; dH 7.43, d, J = 8.8 Hz, H-5; dH 3.77 s, 3H, dC 34.1 (CH3), N-methyl; dH 6.34, d, J = 2.2 Hz, H-4; dH 6.33, d, J = 2.2 Hz, H-2). However, the methoxy group proton and carbon resonances observed in the NMR spectra of 2 have disappeared, having been replaced by the signals of a c,cdimethylallyloxy (prenyloxy) substituent (dH 4.61, 2H, d, J = 6.6 Hz, 2H-1 0 ; dH 5.50, 1H, m, H-2 0 ; dH 1.76, 3H, s, 3H-4 0 ; dH 1.81, 3H, s, 3H-5 0 ; dC 65.2, CH2, C-1 0 ; 118.8, CH, C-2 0 ; 142.3, C, C-3 0 ; 18.3, CH3, C-4 0 ; 25.9, CH3, C5 0 ), which was placed at C-1, as before, on the basis of correlations in the NOESY spectrum between 2H-2 0 and H-2, but not between 2H-2 0 and H-4. As 3-hydroxy-Nmethyl-1-(c,c-dimethylallyloxy)acridone, tegerrardin B 2 is reported here, for the first time, from either natural or synthetic sources, although the 3-prenyloxy isomer vebilocine has previously been isolated from Vepris bilocularis (Wight et Arn.) Engl. (Brader et al., 1996). The known compounds were identified as arborinine 3 (Chakravarti et al., 1953; Bergenthal et al., 1979), evoxanthine 4 (Hughes and Neill, 1949; Rasoanaivo et al., 1999), 1,3-dimethoxy-N-methylacridone 5 (Reisch et al., 1991), evoxine 6 (Moulis et al., 1981; Ali et al., 2001), 4,8-dimethoxy-7-(c,c-dimethylallyloxy)furo[2,3-b]furoquinoline 7 (Bessonova et al., 1974; Al-Rehaily et al., 2003) and tecleanone 8 (Casey and Malhotra, 1975; Waterman, 1975) by comparison of their physical properties and spectral data with the literature values. As rutaceaeus taxa often feature as antimalarials or febrifuges in African traditional medicine (Watt and Breyer-Brandwijk, 1962; Kokwaro, 1976; Neuwinger, 2000), and the significant antiplasmodial activity of a variety of both furoquinoline and acridone alkaloids has earlier been demonstrated (Nkunya, 1992; Basco et al., 1994; Weniger et al., 2001), compounds 1–8 were tested against the CQS D10 strain of P. falciparum. While compounds 2 and 8 were found to be completely inactive, compounds 1, 3 and 4–7 displayed mild activity, with IC50 values of 12.3, 95.3, 70.6, 46.8, 24.5 and 132.4 lM, respectively, against a value of 57.5 nM for CQ as positive control. At 12.3 lM, the activity of arborinine 3 compares reasonably with values of 2.5, 5.3 and 11.1 lM recently reported for three acridones from Swinglea glutinosa Merr. against a Nigerian CQS strain (Weniger et al., 2001), while the 24.5 lM of evoxine 6 makes it more active than haplopine, at 38.8 lM the most active of five furoquinolines tested against the Honduran CQS strain HB3 (Basco et al., 1994). Although numerous studies on the cytotoxicity of acridones against a variety of cell lines have been carried out (Su et al., 1992; Su and Chou, 1994; Kawaii et al., 1999; Teng et al., 2005), Weniger et al. (2001) remains, to our knowledge, the only investigation to date in which antiplasmodial activity and cytotoxicity were simultaneously established. Selectivity indices for the four compounds evaluated were 0.3 and 0.5 for those compounds with a methoxy group at C-4, compared to 9.0 and 7.7 for those without. As some 65% of the more than 150 acridone alkaloids identified to date (Dictionary of Natural Products, 2006) fall into this category, there is scope for much future study. In contrast, the furoquinoline alkaloids have been much less investigated, with only one cytotoxicity study (Chen et al., 2003) to date. No inferences can thus currently be made about this group of compounds. Whereas Dagne et al. (1988) recognized two groups within the genus Teclea, defined by the production of either acridone or furoquinoline alkaloids, both the current report on T. gerrardii and earlier ones on T. natalensis (Pegel and Wright, 1969; Tarus et al., 2005) indicate that at least the southern African representatives produce both alkaloid classes. As all of the constituent classes isolated in the present investigation have previously been recorded from the genus Teclea (Dagne et al., 1988), only minor 665 A.F. Kamdem Waffo et al. / Phytochemistry 68 (2007) 663–667 extensions of the biosynthetic range are evident, and as such no new subtribal or subfamilial chemotaxonomic insights are revealed. However, the two novel acridone alkaloids (tegerrardins A-B 1–2) may presently be considered taxonomic markers for T. gerrardii. (70 eV) m/z (rel. int.) 255 (100), 226 (29), 212 (9), 128 (3), 113 (5); 1H NMR spectral data (400 MHz, CDCl3) dH 8.39 (1H, d, J = 8.1 Hz, H-8), 7.65 (1H, m, H-6), 7.43 (1H, d, J = 8.6 Hz, H-5), 7.24 (1H, m, H-7), 6.24 (1H, d, J = 2.2 Hz, H-2), 6.23 (1H, d, J = 2.2 Hz, H-4), 3.86 (3H, s, 1-OCH3), 3.73 (3H, s, N-CH3); 13C NMR spectral data (100 MHz, CDCl3) Table 1. 3. Experimental 3.1. General Melting points were determined on a Kofler micro-hot stage melting point apparatus and are uncorrected. NMR spectra were recorded at room temperature on a 400 MHz Varian UNITY-INOVA spectrometer. 1H NMR spectra were referenced against the CHCl3 signal at dH 7.27, and 13C NMR spectra against the corresponding signal at dC 77.0. Coupling constants are given in Hz. IR spectra were recorded on a Nicolet Impact 400D Fourier-transform infrared (FT-IR) spectrometer, using NaCl windows with CHCl3 as solvent against an air background. LREIMS and HREIMS were taken on Perkin–Elmer 6890Agilent 5975 GCMS and Micromass VG 70 SEQ instruments, respectively. 3.2. Plant material Stem bark from a cultivated specimen of T. gerrardii I.Verd. was sourced in Durban, South Africa. A voucher (Crouch 1045, NH) has been lodged for verification purposes. 3.3. Extraction and isolation of compounds The air-dried, ground stem bark material of T. gerrardii (800 g) was extracted for 72 h each with hexane, CH2Cl2 and MeOH at room temperature, affording 15.1, 30.6, and 65.7 g of extract, respectively, on concentration under reduced pressure. A 1H NMR spectrum of the MeOH extract showed it to contain mostly sugars and it was not investigated further, while the hexane and CH2Cl2 extracts were combined on the basis of similar TLC profiles. Repeated combinations of vacuum liquid and gravity column chromatography on Merck 7729 and 9385 silica gels, and PTLC on aluminium backed analytical TLC (Merck 5554) plates, using hexane:EtOAc:MeOH mixtures, afforded tegerrardins A 1 (7.2 mg) and B 2 (5.0 mg), together with arborinine 3 (85.0 mg), evoxanthine 4 (50.0 mg), 1,3dimethoxy-N-methylacridone 5 (74.1 mg), evoxine 6 (4.0 mg), 7-(c,c-dimethylallyloxy)-c-fagarine 7 (6.0 mg) and tecleanone 8 (1.219 g). 3.3.1. 3-Hydroxy-1-methoxy-N-methylacridone, tegerrardin A1 Pale yellow powder; m.p. 158–159 °C, mmax(NaCl) cm 1 3449, 1639, 1600, 1461, 1329, 1228, 1159; HREIMS (70 eV) m/z 255.0896 (calc. for C15H13NO3 255.0895); EIMS 3.3.2. 3-Hydroxy-N-methyl-1-(c,cdimethylallyloxy)acridone, tegerrardin B 2 Pale yellow gum, mmax(NaCl) cm 1 3450, 1637, 1600, 1459, 1331, 1228, 1150; HREIMS (70 eV) m/z 309.1358 (calc. for C19H19NO3 309.1365); EIMS (70 eV) m/z (rel. int.) 309 (27), 242 (22), 241 (100), 212 (12), 204 (30), 189 (24), 175 (22), 161 (10), 148 (10), 115 (11), 95 (16); 1H NMR spectral data (400 MHz, CDCl3) dH 8.39 (1H, d, J = 8.1 Hz, H-8), 7.71 (1H, m, H-6), 7.43 (1H, d, J = 8.8 Hz, H-5), 7.27 (1H, m, H-7), 6.34 (1H, d, J = 2.2 Hz, H-4), 6.33 (1H, d, J = 2.2 Hz, H-2), 5.50 (1H, m, H-2 0 ), 4.61 (2H, d, J = 6.6 Hz, 2H-1 0 ), 3.77 (3H, s, N– CH3), 1.81 (3H, s, 3H-5 0 ), 1.76 (3H, s, 3H-4 0 ); 13C NMR spectral data (100 MHz, CDCl3) Table 1. 3.4. Antiplasmodial assay All samples were tested in duplicate on a single occasion against a chloroquine sensitive (CQS) strain of Plasmodium falciparum (D10). Continuous in vitro cultures of asexual erythrocyte stages of P. falciparum were maintained using a modified method of Trager and Jensen (1976). Quantitative assessment of antiplasmodial activity in vitro was determined via the parasite lactate dehydrogenase assay using a modified method described by Makler et al. (1993). The compounds were prepared to a 2 mg/mL stock solution in 10% methanol, 10% ethanol or 10% DMSO. ChloTable 1 13 C NMR spectral data for tegerrardins A 1 and B 2 Carbon 1 1 2 3 4 5 6 7 8 9 4a 1a 8a 5a 1-OCH3 N–CH3 10 20 30 40 50 166.0 89.9 165.8 94.0 114.5 134.0 121.4 126.6 180.6 144.6 105.2 120.9 142.3 55.5 34.0 – – – – – a 2 (C)a (CH) (C)a (CH) (CH) (CH) (CH) (CH) (C) (C) (C) (C) (C) (CH3) (CH3) values interchangeable within column. 165.4 94.5 166.0 90.9 114.4 134.1 121.4 126.8 180.8 144.7 105.4 121.4 142.3 – 34.1 65.2 118.8 142.3 18.3 25.9 (C) (CH) (C) (CH) (CH) (CH) (CH) (CH) (C) (C) (C) (C) (C) (CH3) (CH2) (CH) (C) (CH3) (CH3) 666 A.F. Kamdem Waffo et al. / Phytochemistry 68 (2007) 663–667 roquine (CQ) was used as the reference drug in all experiments. Compounds were stored at 20 °C until use. A full dose–response was performed with a starting concentration of 100 lg/mL, which was serially diluted 2-fold in complete medium to give 10 concentrations; with the lowest concentration being 0.195 lg/mL. The same dilution technique was used for all samples. CQ was tested at a starting concentration of 100 ng/mL. The highest concentration of solvent to which the parasites were exposed to had no measurable effect on the parasite viability (data not shown). The 50% inhibitory concentration (IC50) values were obtained using a non-linear dose–response curve fitting analyses via GraphPad Prism v.4.0 software. Acknowledgements We thank Mr. Dilip Jagjivan for the running of NMR spectra, Mr. Bret Parel and Mr. Tommy van der Merwe for GCMS and HRMS, respectively, Carmen Lategan for overseeing the bioassays, and the University of KwaZuluNatal and the National Research Foundation (NRF) for financial aid. Dr. Alain Kamdem Waffo gratefully acknowledges a Post-doctoral Fellowship from the NRF. The KwaZulu-Natal Herbarium (SANBI) kindly permitted harvesting of plant material. Members of the staff of the Mary Gunn Library (SANBI) are thanked for facilitating access to the literature. References Ali, M.S., Pervez, M.K., Saleem, M., Tareen, R.B., 2001. Haplophytin-A and B: the alkaloidal constituents of Haplophyllum acutifolium. Phytochemistry 57, 1277–1280. Al-Rehaily, A.J., Ahmad, M.S., Muhammad, I., Al-Thukair, A.A., Perzanowski, H.P., 2003. Furoquinoline alkaloids from Teclea nobilis. Phytochemistry 64, 1405–1411. Basco, L.K., Mitaku, S., Skaltsounis, A.L., Ravelomanantsoa, N., Tillequin, F., Koch, M., Le Bras, J., 1994. In vitro activities of furoquinoline and acridone alkaloids against Plasmodium falciparum. Antimicrobial Agents and Chemotherapy 38, 1169–1171. Bergenthal, D., Mester, I., Rozsa, Zs., Reisch, J., 1979. Studies in the field of natural product chemistry. Part 63. Carbon-13 NMR spectra of acridone alkaloids. Phytochemistry 18, 161–163. Bessonova, I.A., Akhmedzhanova, V.I., Yunusov, S.U., 1974. 7-Isopentenylhydroxy-c-fagarine from Haplophyllum perforatum. Khimiya Prirodnykh Soedinenii, 677–678. Brader, G., Bacher, M., Greger, H., Hofer, O., 1996. Pyranoquinolones and acridones from Vepris bilocularis. Phytochemistry 42, 881–884. Casey, A.C., Malhotra, A., 1975. Tecleanone. New alkaloid from Teclea grandifolia. Tetrahedron Letters, 401–404. Chakravarti, D., Chakravarti, R.N., Chakravarti, S.C., 1953. Alkaloids of Glycosmis arborea. I. Isolation of arborine and arborinine. Structure of arborine. Journal of the Chemical Society, 3337–3340. Chen, J.-J., Duh, C.-Y., Huang, H.-Y., Chen, I.-S., 2003. Furoquinoline alkaloids and cytotoxic constituents from the leaves of Melicope semecarpifolia. Planta medica 69, 542–546. Dagne, E., Yenesew, A., Waterman, P.G., Gray, A.I., 1988. The chemical systematics of the Rutaceae, subfamily Toddalioideae, in Africa. Biochemical Systematics and Ecology 16, 179–188. Dictionary of Natural Products on CD-ROM, 2006. Chapman Hall/CRC Press/Hampden Data Services, Ltd. Engler, A., 1931. Rutaceae, Second ed.. In: Engler, A., Prantl, K. (Eds.), Die natürlichen pflanzenfamilien, 19a Engelmann, Leipzig, pp. 187– 359. Hlubucek, J.R., Ritchie, E., Taylor, W.C., 1970. Synthesis of acronycine. Australian Journal of Chemistry 23, 1881–1889. Hughes, G.K., Neill, K.G., 1949. Alkaloids of the Australian Rutaceae: Evodia xanthoxyloides. I. Evoxanthine. Australian Journal of Scientific Research 2A, 429–436. Hutchings, A., Scott, A.H., Lewis, G., Cunningham, A., 1996. Zulu medicinal plantsAn inventory. University of Natal Press, Pietermaritzburg, p. 153.. Kawaii, S., Tomono, Y., Katase, E., Ogawa, K., Yano, M., Takemura, Y., Ju-ichi, M., Ito, C., Furukawa, H., 1999. The antiproliferative effect of acridone alkaloids on several cancer cell lines. Journal of Natural Products 62, 587–589. Kokwaro, J.O., 1976. Medicinal plants of East Africa. East African Literature Bureau, Nairobi. Makler, M.T., Ries, J.M., Williams, J.A., Bancroft, J.E., Piper, R.C., Gibbins, B.L., Hinrichs, D.J., 1993. Parasite lactate dehydrogenase as an assay for Plasmodium falciparum drug sensitivity. Journal of the American Society of Tropical Medicine and Hygiene 48, 739–741. Mbala, M.B., 2006. A Chemical Investigation of Two South African Vepris species. M.Sc. Thesis, University of KwaZulu-Natal, Howard College Campus. Moulis, C., Gleye, J., Fouraste, I., Stanislas, E., 1981. New furoquinolines from Monnieria trifolia. Planta Medica 42, 400–402. Naidoo, D., Coombes, P.H., Mulholland, D.A., Crouch, N.R., van den Bergh, A.J.J., 2005. N-substituted acridone alkaloids from Toddaliopsis bremekampii (Rutaceae: Toddalioideae) of south-central Africa. Phytochemistry 66, 1724–1728. Neuwinger, H.D., 2000. African traditional medicine: a dictionary of plant use and applications. Medpharm Scientific Publishers, Stuttgart, Germany, p. 589.. Nkunya, M.H.H., 1992. Progress in the search for antimalarials. NAPRECA Monograph Series No. 4. NAPRECA, Addis Ababa University, Ethiopia, p. 36 Pegel, K.H., Wright, W.G., 1969. South African Plant extractives. Part II. Alkaloids of Teclea natalensis. Journal of Chemical Society (C), 2327– 2329. Rasoanaivo, P., Federici, E., Palazzino, G., Galeffi, C., 1999. Acridones of Vepris sclerophylla: their 13C NMR data. Fitoterapia 70, 625–627. Reisch, J., Herath, H.M.T.B., Kumar, N.S., 1991. Natural product chemistry. Convenient synthesis of isoacronycine and some other new acridone derivatives. Liebigs Annalen der Chemie 143, 685–689. Su, T.-L., Chou, T.-C., 1994. Experimental antitumor activity of acridone alkaloids, acronycine and glyfoline. Chinese Pharmaceutical Journal (Taipei, Taiwan) 46, 371–391. Su, T.-L., Kohler, B., Chou, T.-C., Chun, M.-W., Watanabe, K.-A., 1992. Synthesis of the acridone alkaloids glyfoline and congeners. Structure– activity relationship studies of cytotoxic acridones. Journal of Medicinal Chemistry 35, 2703–2710. Tarus, P.K., Coombes, P.H., Crouch, N.R., Mulholland, D.A., Moodley, B., 2005. Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis. Phytochemistry 66, 703–706. Tarus, P.K., Coombes, P.H., Crouch, N.R., Mulholland, D.A., 2006. Benzo[c]phenanthridine alkaloids from stem bark of the Forest Knobwood, Zanthoxylum davyi (Rutaceae). South African Journal of Botany 72, 555–558. Teng, W.-Y., Huang, Y.-L., Shen, C.-C., Huang, R.-L., Chung, R.-S., Chen, C.-C., 2005. Cytotoxic acridone alkaloids from the stem bark of Citrus maxima. Journal of the Chinese Chemical Society (Taipei, Taiwan) 52, 1253–1255. Trager, W., Jensen, J.B., 1976. Human malaria parasite in continuous culture. Science 193 (4254), 673–675. Verdoorn, I.C., 1926. Revision of the African Toddalieae. Kew Bulletin, 389–416. A.F. Kamdem Waffo et al. / Phytochemistry 68 (2007) 663–667 Victor, J.E., 2000. Rutaceae. In: Leistner, O.A. (Ed.), Seed plants of southern Africa: families and genera. Strelitzia, 10. National Botanical Institute, Pretoria, pp. 495–499. Waterman, P.G., 1973. Alkaloids and triterpenes from the African Toddalioideae. Biochemical Systematics and Ecology 1, 153–161. Waterman, P.G., 1975. Tecleanone from Diphasia klaineana and Teclea verdoorniana. Phytochemistry 14, 2092–2093. Waterman, P.G., Meshal, I.A., Hall, J.B., Swaine, M.D., 1978. Biochemical systematics and ecology of the Toddalioideae in the central part of 667 the West African forest zone. Biochemical Systematics and Ecology 6, 239–245. Watt, J.M., Breyer-Brandwijk, M.G., 1962. Medicinal and poisonous plants of southern and eastern Africa. E&S Livingstone Ltd., London and Edinburgh. Weniger, B., Um, B.-H., Valentin, A., Estrada, A., Lobstein, A., Anton, R., Maille, M., Sauvain, M., 2001. Bioactive acridone alkaloids from Swinglea glutinosa. Journal of Natural Products 64, 1221–1223.