Ángela I. Calderón

Screening of Latin American Plants for Cytotoxic Activity

Abstract The SRB cytotoxicity assay was used to screen plant extracts, in a collaborative multinational OAS project involving Argentina, Bolivia, Colombia, Costa Rica, Guatemala, Nicaragua and Panama, against breast (MCF-7), lung (H-460), and central nervous system (SF-268) human cancer cell lines. Out of 310 species tested, 23 (7.4%) plants showed cytotoxic activity at GI50 values ≤10 µg/ml. The most active plants were Thevetia ahouai., Physalis viscosa., Piper jacquemontianum., Piper barbatum., Senna occidentalis., Tovomita longifolia., and Lippia cardiostegia.. Blepharocalyx salicifolius. and Senna occidentalis. were selectively active against one cell line, SF-268 or MCF-7, respectively. Within the framework of this project, 14 compounds have been isolated, 5 new (4 benzophenones, coumarin) and 9 known to the literature. But only the bioassay-guided fractionation of the active extract of Piper barbatum. leaves, which led to the isolation of three known compounds: (2′E., 6′E.)-2-farnesyl-1,4-benzoquinone (1), (2′E., 6′E.)-2-farnesylhydroquinone (2), and dictyochromenol (3), is reported here. The chemical structures of 1 and 2 were determined by spectral means (1D, 2D NMR, MS) and chemical data. Among these three, (2′E., 6′E.)-2-farnesyl-1,4-benzoquinone was the most active (MCF-7 GI50 = 1.8 µg/ml; H-460 GI50 = 4.8 µg/ml; SF-268 GI50 = 3.5 µg/ml).

Evaluation of Larvicidal and in Vitro. Antiparasitic Activities of Plants in a Biodiversity Plot in the Altos de Campana National Park, Panama

Abstract This TDR/WHO project was carried out from 2003 to 2005 in an 0.1-ha biodiversity plot in the Altos de Campana National Park to discover novel active antiparasitic and larvicidal compounds in Panamanian plants. One-hundred-fifty organic plant extracts representing 43 families, 73 genera, and 93 species were tested in a panel of antimalarial (Plasmodium falciparum. W2, chloroquine resistant), antileishmanial (Leishmania mexicana. amastigotes), antitrypanosomal (Trypanosoma cruzi. trypomastigotes), and larvicidal (Aedes aegypti.) screens. Of these 150 plant extracts, two (1.3%) (Talisia nervosa. and Topobea parasitica.) showed significant antimalarial activity (IC50 values < 10 µg/ml), two (1.3%) (Cestrum megalophyllum. and Zanthoxylum acuminatum.) weak antileishmanial activity (IC50 values ranging from 10 to 20 µg/ml), one (0.6%) (Zanthoxylum acuminatum.) weak antitrypanosomal activity (IC50 values ranging from 10 to 20 µg/ml), and one (0.6%) (Piper fimbriulatum.) larvicidal activity (LC100 values < 30 µg/ml). Ethyl gallate (1) and methyl gallate (2) were isolated from stems of Talisia nervosa. by bioassay-guided fractionation. Both (1) and (2) showed weak in vitro. antiplasmodial activity against P. falciparum. (IC50 35.3 µM and IC50 38.0 µM, respectively), but both compounds were less active than chloroquine (IC50 0.088 µM). Moreover, compounds (1) (IC50 33.1 µM) and (2) (IC50 33.6 µM) showed weakly antileishmanial activity (miltefosine: IC50 0.5 µM), but they were not cytotoxic to Vero mammalian cells.

A New Larvicidal Lignan from Piper fimbriulatum

Abstract A new lignan, 3,4,5′-trimethoxy-3′,4′-methylenedioxy-7,9′:7′,9 diepoxylignan (1) (6-[4-(3,4-dimethoxy-phenyl)-tetrahydro-furo[3,4-c.]furan-1-yl]-4-methoxy-benzo[] dioxole) together with two known lignans, 7′-epi.-sesartemin (2) and diayangambin (3), and a known flavonoid, 5-hydroxy-7,4′-dimethoxyflavone (4), were isolated from the leaves of Piper fimbriulatum. C. DC. Their structures were assigned by a combination of one- and two-dimensional NMR techniques. 7′-epi.-Sesartemin (2) showed the highest larvicidal activity against Aedes aegypti. (LC100 17.6 µg/ml) and weak antiplasmodial (IC50 7.0 µg/ml) and antitrypanosomal (IC50 39.0 µg/ml) activities. None of the compounds was active against Leishmania mexicana..

In vitro cytotoxicity of 11 Panamanian plants.

Thirty-five crude extracts from 11 Panamanian plants, distributed in 10 genera and five families, were evaluated for their in vitro cytotoxicity. Four extracts exhibited an inhibition of cellular growth at IC(50) values lower than 25 microg/ml which was considered a significant activity.

Occurrence of taxiphyllin and 3, 3'-di-O-methylellagic acid 4'-β-D-glucoside in Henriettella fascicularis

The chemistry of Melastomataceae is poorly known. According to previous studies, this family is characterized by tannins (Cronquist, 1981, 1988). Lichexanthone, palmitic acid, betulinic acid, ~-sitosterol, (-)-pinoresinol, 4,5,7 -trihydroxy-6,8-dimethylisoflavone and (2£,6S)-6-( lR,5Z,3aS,9R, 10Z, 12aR)-1,2,3,3a,4,7,8,9,12, 12a-decahydro-9hydroxy-3a,6, 1 O-trimethylcyc1opentanocycloundecen-l-yl]-2-methyl-hept-2-enoic acid were reported from the dichloromethane extract of branches of H. fascicularis (Calder6n et aI., 2002). To our knowledge this is the only study reported so far about the chemical composition of Henriettella species

Anti-Inflammatory and Analgesic Activities of Vochysia ferruginea

Anti-inflammatory activity of a methanol extract of the leaves of Vochysia ferruginea Mart. (Vochysiaceae) was determined in the rat paw edema test. At doses of 250 and 500 mg/kg, i.p., the extract reduced edema significantly (p < 0.01) compared with indomethacin (10 mg/kg). It also showed significant dose-dependent analgesic activity (0.3–100 mg/kg) in mice (p < 0.05), compared with acetaminophen (130 mg/kg), and inhibitory activity with cyclooxygenase (COX-1) (72% at 70 mg/ml), compared with indomethacin (2.3 mM). An ulcerogenic effect was observed when the extract was administered to rats.

Screening of Anticancer and Immunomodulatory Activities of Panamanian Plants

Fifty-one extracts, from six Panamanian plants species selected on the basis of their toxicities against Artemia salina, belonging to five families and five genera, were screened for their in vitro anticancer (TK-10, UACC-62, MCF-7) and immunomodulatory activities [inhibition of complement, classical (CP) and alternative (AP) complement pathway and lymphoproliferation]. The results showed that 9 (17.6%) of 51 extracts presented anticancer activity against cancer cell lines, while 28 (54.9%) of 51 extracts stimulated normal spleen cells proliferation, and 25 (49.0%) inhibited in vitro lymphoid tumor cell growth. Finally, 7 (19.4%) and 10 (27.8%) out of 36 extracts showed high and moderate anticomplementary activity on CP, respectively. Moreover, out of 36 extracts, 1 (2.8%) produced higher inhibition while 4 (11.1%) showed moderate inhibition in the alternate pathway. The dichloromethane, methanolic and aqueous extracts from the leaf (3.0, 3.2, 4.2) and branch (3.5, 5.7, 5.8) of Trichospermum galeottii and from the leaf (2.4, 2.5, 5.6) and stem (2.3, 2.3, 4.7) of Sauraria yasicae were the most active immunomodulatory plants. The dichloromethane extract from the root of Morinda panamensis (8.7, 4.4, 6.3) was active against the three cancer cell lines, while the dichloromethane extract from the bark of Trichospermum galeottii(TK-10 = 3.4,UACC-62 = 9.4) and the bark of Morinda panamensis (UACC-62 = 5.5, MCF-7 = 5.9) as well as the methanolic extract from the root of Morinda rojoc (UACC-62 = 9.2, MCF-7 = 9.4) exhibited selectivity against two cancer cell lines.

Long-term mortality in patients with a prolonged postoperative intensive care unit (PICU) stay

Non-cardiac surgical patients undergoing major surgery are progressively older and with multiple associated comorbidity. A worse baseline status and complicated postoperative course is usually assumed in patients who die in the postoperative intensive care unit (PICU). This study evaluates mortality in patients with prolonged ICU stay and try to identify differences in subjects characteristics and to determine risk factors for mortality among those dying in ICU.

Taxiphyllin from Henriettella fascicularis

(2R)-alpha-(beta-D-Glucopyranosyloxy)-4-hydroxybenzeneacetonitrile (taxiphyllin) dihydrate, C(14)H(17)NO(7) x 2H(2)O, is a naturally occurring cyanogenetic glycoside which has been isolated from Henriettella fascicularis (Sw.) C. Wright (Melastomataceae). Its structure is stabilized by a wealth of intermolecular O-H...O and O-H...N hydrogen bonds spun into a three-dimensional network. Further stabilization arises from an intramolecular O-H...O bond and weak intermolecular C-H...O interactions. The very anisotropic growth speeds of the basal pinacoids from methanol mirror a certain structural inhomogeneity.