{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:32:37Z","timestamp":1781724757891,"version":"3.54.5"},"reference-count":43,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T00:00:00Z","timestamp":1369785600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>A new indole alkaloid, 12-hydroxy-N-acetyl-21(N)-dehydroplumeran-18-oic acid (13), and 11 known indole alkaloids: 3,4,5,6-tetradehydro-\u03b2-yohimbine (3), 19(E)-hunteracine (4), b-yohimbine (5), yohimbine (6), 19,20-dehydro-17-a-yohimbine (7), uleine (10), 20-epi-dasycarpidone (11), olivacine (8), 20-epi-N-nor-dasycarpidone (14),  N-demethyluleine (15) and 20(E)-nor-subincanadine E (12) and a boonein d-lactone 9, ursolic acid (1) and 1D,1O-methyl-chiro-inositol (2) were isolated from the EtOH extracts of different parts of Aspidosperma ulei Markgr. (Apocynaceae). Identification and structural elucidation were based on IR, MS, 1H- and 13C-NMR spectral data and comparison to literature data. The antiplasmodial and antimalarial activity of 1, 5, 6, 8, 10 and 15 has been previously evaluated and 1 and 10 have important in vitro and in vivo antimalarial properties according to patent and\/or scientific literature. With the aim of discovering new antiplasmodial indole alkaloids, 3, 4, 11, 12 and 13 were evaluated for  in vitro inhibition against the multi-drug resistant K1 strain of the human malaria parasite Plasmodium falciparum. IC50 values of 14.0 (39.9), 4.5 (16.7) and 14.5 (54.3) mg\/mL (mM) were determined for 3, 11 and 12, respectively. Inhibitory activity of 3, 4, 11, 12 and 13 was evaluated against NIH3T3 murine fibroblasts. None of these compounds exhibited toxicity to fibroblasts (IC50 &gt; 50 mg\/mL). Of the five compounds screened for in vitro antiplasmodial activity, only 11 was active.<\/jats:p>","DOI":"10.3390\/molecules18066281","type":"journal-article","created":{"date-parts":[[2013,5,29]],"date-time":"2013-05-29T11:59:57Z","timestamp":1369828797000},"page":"6281-6297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Chemical Composition of Aspidosperma ulei Markgr. and Antiplasmodial Activity of Selected Indole Alkaloids"],"prefix":"10.3390","volume":"18","author":[{"given":"Zelina","family":"Dos Santos Torres","sequence":"first","affiliation":[{"name":"Instituto Nacional de Pesquisas da Amaz\u00f4nia, Caixa Postal 2223 - CEP 69080-971, Manaus, Amazonas, Brasil"},{"name":"Universidade Federal do Cear\u00e1, Caixa Postal 12.200 - CEP 60021-940, Fortaleza, Cear\u00e1, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edilberto","family":"Silveira","sequence":"additional","affiliation":[{"name":"Universidade Federal do Cear\u00e1, Caixa Postal 12.200 - CEP 60021-940, Fortaleza, Cear\u00e1, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luiz","family":"Rocha e Silva","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Pesquisas da Amaz\u00f4nia, Caixa Postal 2223 - CEP 69080-971, Manaus, Amazonas, Brasil"},{"name":"Universidade Federal do Amazonas, Avenida General Rodrigo Ot\u00e1vio Jord\u00e3o Ramos, 3000,  CEP 69077-000 Campus Universit\u00e1rio, Manaus, Amazonas, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-2812","authenticated-orcid":false,"given":"Emerson","family":"Lima","sequence":"additional","affiliation":[{"name":"Universidade Federal do Amazonas, Avenida General Rodrigo Ot\u00e1vio Jord\u00e3o Ramos, 3000,  CEP 69077-000 Campus Universit\u00e1rio, Manaus, Amazonas, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marne","family":"De Vasconcellos","sequence":"additional","affiliation":[{"name":"Universidade Federal do Amazonas, Avenida General Rodrigo Ot\u00e1vio Jord\u00e3o Ramos, 3000,  CEP 69077-000 Campus Universit\u00e1rio, Manaus, Amazonas, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"De Andrade Uchoa","sequence":"additional","affiliation":[{"name":"Universidade Federal do Cear\u00e1, Caixa Postal 12.200 - CEP 60021-940, Fortaleza, Cear\u00e1, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raimundo","family":"Filho","sequence":"additional","affiliation":[{"name":"Universidade Estadual do Norte Fluminense Darcy Ribeiro, CEP 28013-602 Campos dos Goytacazes, Rio de Janeiro, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian","family":"Pohlit","sequence":"additional","affiliation":[{"name":"Instituto Nacional de Pesquisas da Amaz\u00f4nia, Caixa Postal 2223 - CEP 69080-971, Manaus, Amazonas, Brasil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,5,29]]},"reference":[{"key":"ref_1","unstructured":"(2011). World Malaria Report, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1136\/bmj.329.7475.1156","article-title":"Clinical Review. Traditional herbal medicines for malaria","volume":"329","author":"Willcox","year":"2004","journal-title":"Med. J."},{"key":"ref_3","unstructured":"Milliken, W. (1997). Plants for Malaria. Plants for Fever, The Royal Botanic Gardens."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1590\/S0001-37652012000400005","article-title":"In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil)","volume":"84","author":"Dolabela","year":"2012","journal-title":"An. Acad. Bras. Ci\u00ean."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1590\/S0100-40422007000400037","article-title":"Alcal\u00f3ides ind\u00f3licos isolados de esp\u00e9cies do g\u00eanero Aspidosperma (Apocynaceae)","volume":"30","author":"Pereira","year":"2007","journal-title":"Qu\u00edm. Nova"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1590\/S1516-05722009000100015","article-title":"Atividade biol\u00f3gica e alcal\u00f3ides ind\u00f3licos do g\u00eanero Aspidosperma (Apocynaceae): uma revis\u00e3o","volume":"11","author":"Oliveira","year":"2009","journal-title":"Rev. Bras. Plantas Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1590\/S0100-40422010000200010","article-title":"Alcal\u00f3ides ind\u00f3licos das cascas de Aspidosperma vargasii e A. desmanthum","volume":"33","author":"Henrique","year":"2010","journal-title":"Qu\u00edm. Nova"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4433","DOI":"10.1021\/ja01525a084","article-title":"The structure of uleine","volume":"81","author":"Warnhoff","year":"1959","journal-title":"J. Am. Chem. Soc."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2492","DOI":"10.1021\/ja00739a022","article-title":"Stereospecific syntheses of uleine and epiuleine","volume":"93","author":"Gould","year":"1971","journal-title":"J. Am. Chem. Soc."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1078\/0944-7113-00094","article-title":"Antiplasmodial activity of Aspidosperma indole alkaloids","volume":"9","author":"Sauvain","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_11","unstructured":"Dominique, M., and Roland, M. Use of uleine for the prevention and\/or the treatment of infectious diseases. (WO 2011160684 A1 20111229), PCT Int. Appl."},{"key":"ref_12","unstructured":"Oliveira, A.B. (2011). Standardized extracts and fractions of husks of Aspidosperma parvifolium and\/or ulein for pharmaceutical use. (PI BR 20095584 A2 20110823), Brazilian Patent."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Oliveira, A.B., Dolabela, M., P\u00f3voa, M., Santos, C.A.M., and Varotti, F.P. (2010). Antimalarial activity of ulein and proof of its action on the Plasmodium falciparum digestive vacuole. Malaria J., 9, Oral Presentation O9.","DOI":"10.1186\/1475-2875-9-S2-O9"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1590\/S0074-02762007000300016","article-title":"In vitro inhibition of Plasmodium falciparum by substances isolated from Amazonian antimalarial plants","volume":"102","author":"Pohlit","year":"2007","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.phymed.2012.09.008","article-title":"Comparative in vitro and in vivo antimalarial activity of the indole alkaloids ellipticine, olivacine, cryptolepine and a synthetic cryptolepine analog","volume":"20","author":"Montoia","year":"2012","journal-title":"Phytomedicine"},{"key":"ref_16","unstructured":"Uchoa, D.E.A. (2006). Aplica\u00e7\u00e3o de t\u00e9cnicas contempor\u00e2neas de resson\u00e2ncia magn\u00e9tica nuclear no estudo fitoqu\u00edmico de Aspidosperma ulei Markgf. [Ph.D. Thesis, Universidade Federal do Cear\u00e1]."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0040-4039(01)82723-4","article-title":"Alkaloids from Aspidosperma australe Mull Argov. Relationship of olivacine to u-alkaloid C. The structure of olivacine and u-alkaloid C (guatambuine)","volume":"7","author":"Ondetti","year":"1959","journal-title":"Tetrahedron Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1002\/mrc.1214","article-title":"Spectral assignments and reference data","volume":"41","author":"Seebacher","year":"2003","journal-title":"Magn. Reson. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1590\/S0100-40422011000100008","article-title":"Constituintes qu\u00edmicos de Hyptidendron canun (Pohl ex Benth.) R. Harley (Lamiaceae)","volume":"34","author":"Lemes","year":"2011","journal-title":"Qu\u00edm. Nova"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1107\/S1600536806037019","article-title":"L-(+)-Bornesitol","volume":"63","author":"Endringer","year":"2007","journal-title":"Acta Crystallogr. Sect. E"},{"key":"ref_21","first-page":"705","article-title":"Anhydronium bases from Rauvolfia serpentina","volume":"61","author":"Waschsmuth","year":"2002","journal-title":"Phytomedicine"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1021\/ja00428a044","article-title":"General methods of synthesis on indole alkaloids. 14. Short routes of construction of yohimboid and ajmalicinoid alkaloid systems and their 13C nuclear magnetic resonance spectral analysis","volume":"98","author":"Wenkert","year":"1976","journal-title":"J. Am. Chem. Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.phymed.2011.03.010","article-title":"Indole and aminoimidazole moieties appear as key structural units in antiplasmodial molecules","volume":"18","author":"Passemar","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_24","unstructured":"Hu, Y., and Coates, A.R.M. (2012). Novel combination for treatment of microbial infections. (WO 2012032360 CA 2809203), Patent PCT Int. Appl."},{"key":"ref_25","first-page":"3785","article-title":"Alkaloids from leaves and root bark of Ervatamia hirta","volume":"30","author":"Pascale","year":"1991","journal-title":"Phytomedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1021\/jo01041a001","article-title":"The alkaloids of Hunteria eburnea Pichon. II: The quaternary bases","volume":"28","author":"Bartlett","year":"1963","journal-title":"J. Org. Chem."},{"key":"ref_27","first-page":"722","article-title":"Hunteracine: The crystal structure of a quaternary alkaloid from Hunteria eburnea Pichon","volume":"12","author":"Burnell","year":"1970","journal-title":"J. Chem. Soc. Chem. Comm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1139\/v74-335","article-title":"Quaternary bases from Hunteria eburnea Pichon","volume":"52","author":"Burnell","year":"1974","journal-title":"Can. J. Chem."},{"key":"ref_29","first-page":"323","article-title":"Research on Africa medicinal plants-IV: Boonein, a new C-9 terpenoid lactone from Alstonia boonei: A possible precursor in the indole alkaloid biogenesis","volume":"39","author":"Nicoletti","year":"1983","journal-title":"Tetrahedron"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1021\/np50026a012","article-title":"Studies on the uleine alkaloids I. Carbon-13-NMR studies on uleine, 20-epiuleine and (4S)-uleine-Nb-oxide","volume":"46","author":"Borris","year":"1983","journal-title":"J. Nat. Prod."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"897","DOI":"10.1590\/S0100-40422004000600011","article-title":"Estudo qu\u00edmico e perfil cromatogr\u00e1fico de Aspidosperma parvifolium A. DC. (\u201cpau-pereira\u201d)","volume":"27","author":"Oliveira","year":"2004","journal-title":"Qu\u00edm. Nova"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8681","DOI":"10.1021\/jo0487101","article-title":"Conjugate additions to phenylglycinol-derived unsaturated \u03b4-lactams enantioselective synthesis of uleine alkaloids","volume":"69","author":"Amat","year":"2004","journal-title":"J. Org. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1016\/0040-4020(96)00033-6","article-title":"Synthetic applications of 2-(1,3-dithian-2-yl) indoles VI. Synthesis of 20-epidasycarpidone","volume":"52","author":"Forns","year":"1996","journal-title":"Tetrahedron"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1021\/jo00093a028","article-title":"Total synthesis of uleine-type and Strychnos alkaloids through a common intermediate","volume":"59","author":"Casamitjana","year":"1994","journal-title":"J. Org. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1590\/S0102-695X2010005000019","article-title":"Isolamento, identifica\u00e7\u00e3o e avalia\u00e7\u00e3o da atividade antileuc\u00eamica de alcal\u00f3ides ind\u00f3licos monoterp\u00eanicos de Tabernaemontana salzmannii (A. DC.), Apocynaceae","volume":"20","author":"Figueiredo","year":"2010","journal-title":"Rev. Bras. Farmacogn."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6449","DOI":"10.1021\/jo025854b","article-title":"Subicanadines A\u2013C, novel quaternary \u00edndole alkaloids from Aspidosperma subincanum","volume":"67","author":"Kobayashi","year":"2002","journal-title":"J. Org. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1016\/0957-4166(96)00359-X","article-title":"An enantioselective synthesis of the Strychnos alkaloid (\u2212)-tubifoline","volume":"7","author":"Amat","year":"1996","journal-title":"Tetrahedron-Asymmetry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/S0957-4166(97)00071-2","article-title":"Total synthesis of the Strychnos indole alkaloids (\u2212)-tubifoline, (\u2212)-tubifolidine and (\u2212)-19,20-dihydroakuammicine","volume":"8","author":"Amat","year":"1997","journal-title":"Tetrahedron-Asymmetr."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Milborrow, B.V., and Djerassi, C. (1969). Alkaloids studies: Part LXI: The structure of twelve new alkaloids from Aspidosperma cylindrocarpon. J. Chem. Soc. C, 417\u2013424.","DOI":"10.1039\/j39690000417"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.3390\/molecules17033025","article-title":"1H and 13C-NMR data of the simplest plumeran indole alkaloids isolated from Aspidosperma species","volume":"17","author":"Vieira","year":"2012","journal-title":"Molecules"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites in continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Rocha e Silva, L.F., Lima, E.S., Vasconcellos, M.C., Aranha, E.S.P., Costa, D.S., Santos, E.V.M., Silva, T.C.M., Morais, S.K.R., Quignard, E.L.J., and Alecrim, M.G.C. (2013). In vitro and in vivo antimalarial activity and cytotoxicity of extracts, fractions and a substance isolated from the Amazonian plant Tachia grandiflora (Gentianaceae). Mem. Inst. Oswaldo Cruz, 108, in press.","DOI":"10.1590\/S0074-02762013000400017"},{"key":"ref_43","first-page":"15211","article-title":"A new rapid and simple non-radioactive assay to monitor and determine the proliferation of lymphocytes: An alternative to [3H] thymidine incorporation assay","volume":"15","author":"Ahmed","year":"1994","journal-title":"J. Immunol. Meth."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/6\/6281\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:47:03Z","timestamp":1760219223000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/6\/6281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5,29]]},"references-count":43,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6]]}},"alternative-id":["molecules18066281"],"URL":"https:\/\/doi.org\/10.3390\/molecules18066281","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,5,29]]}}}