Physangulidines A, B, and C: three new antiproliferative withanolides from Physalis angulata L.

Bioassay-directed fractionation of the whole plant of Physalis angulata L. afforded three new antiproliferative withanolides with an unusual carbon framework: physangulidines A (1), B (2), and C (3). Structures of the three isomeric withanolides were determined by a combination of HRMS, NMR spectroscopic, and X-ray crystallographic methods. Each has shown significant antiproliferative activity against DU145 prostate cancer cells. Physangulidine A (1) was further tested against a wide range of additional cancer cell lines and found to exhibit significant antiproliferative activity.

Cytotoxic and anti-infective phenolic compounds isolated from Mikania decora and Cremastosperma microcarpum.

An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien-19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro-6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6-methoxythymol isobutyrate (3), and acetylschizoginol (4), as well as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes.

Cytotoxic and anti-infective sesquiterpenes present in Plagiochila disticha (Plagiochilaceae) and Ambrosia peruviana (Asteraceae).

A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, Plagiochila disticha and Ambrosia peruviana, led to the isolation and characterization of three ENT-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A ( 1), I ( 2), and R ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their in vitro antileishmanial, trypanocidal, and antituberculosis activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes, as well as against MDR and sensitive strains of Mycobacterium tuberculosis, respectively.

A multipronged approach to the study of peruvian ethnomedicinal plants: a legacy of the ICBG-Peru Project.

A multidisciplinary and international team of scientists was assembled in the early 1990s to conduct an ethnobotanical study of plants used by the Aguaruna people of the Peruvian Amazon forest. The initial ethnobotanical project, carried out under the auspices of an International Cooperative Biodiversity Grant (ICBG), led to the collection of approximately 4000 plant species. Some members of the original team of scientists have continued this collaboration by focusing on potential sources of new anticancer, anti-infective, and wound-healing agents. This effort has uncovered several secondary metabolites representing a wide variety of chemical diversity. In this short review we describe some bioactive compounds of interest as part of our continuing collaboration.

Anti-infective and cytotoxic compounds present in Blepharodon nitidum.

A pharmacological screening of the ethanol extract and fractions of Blepharodon nitidum led to the isolation of fourteen compounds, two of which, 24-hydroperoxycycloart-25-en-3beta-ol and 25-hydroperoxycycloart-23-en-3beta-ol, exhibited in vitro anti- Mycobacterium tuberculosis and antileishmanial activities, as well as significant cytotoxic activity against a panel of human tumor cell lines.

Isolation of cytotoxic metabolites from targeted peruvian amazonian medicinal plants.

The antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2',4'-dihydroxy-6'-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13-acetate (7), respectively. Eight human tumor cell lines and two nontumorigenic cell lines were used in this investigation. Their in vitro activity against Mycobacterium tuberculosis is also reported.

Aegicerin, the first oleanane triterpene with wide-ranging antimycobacterial activity, isolated from Clavija procera.

An ethanol extract of the Peruvian plant Clavija procera, a member of the rare Theophrastaceae family, was fractionated using a colorimetric bioassay-guided protocol against Mycobacterium tuberculosis (MTB), yielding the oleanane triterpenoid aegicerin (1) as the active constituent. Its MIC values ranged between 1.6 and 3.12 microg/mL against 37 different sensitive and resistant MTB strains (1 H37Rv, 21 susceptible clinical isolates, 2 INH-resistant clinical isolates, and 13 MDR clinical isolates).

Polyploid and hybrid evolution in roses east of the Rocky Mountains.

This study investigates the impact of hybridization and polyploidy in the evolution of eastern North American roses. We explore these processes in the Rosa carolina complex (section Cinnamomeae), which consists of five diploid and three tetraploid species. To clarify the status and origins of polyploids, a haplotype network (statistical parsimony) of the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) nuclear gene was estimated for polyploids of the complex and for diploids of section Cinnamomeae in North America. A genealogical approach helped to decipher the evolutionary history of polyploids from noise created by hybridization, incomplete lineage sorting, and allelic segregation. At the diploid level, species west of the Rocky Mountains are distinct from eastern species. In the east, two groups of diploids were found: one consists of R. blanda and R. woodsii and the other of R. foliolosa, R. nitida, and R. palustris. Only eastern diploids are involved in the origins of the polyploids. Rosa arkansana is derived from the blanda-woodsii group, R. virginiana originated from the foliolosa-nitida-palustris group, and R. carolina is derived from a hybrid between the two diploid groups. The distinct origins of these polyploid taxa support the hypothesis that the three polyploids are separate species.

Oleanene constituents of Lantana cujabensis.

A new compound, 3beta,25-epoxy-3alpha-hydroxy-22beta-isobutanoyloxyolean-12-ene-28-oic acid (1), and two known triterpenoids lantanilic acid (2) and camaric acid (3) were isolated from the stem and leaves of Lantana cujabensis. Their structures were elucidated by spectroscopic methods. The ethanol extracts did not show significant in vitro antiplasmodial activity against chloroquine-sensitive or resistant strains of Plasmodium falciparum.

Natural antimycobacterial metabolites: current status.

Over the years the introduction of very effective drugs has revolutionized the treatment of tuberculosis. In recent years, however, emerging multiple drug resistance has become a major threat and thus calls for an urgent search for new and effective treatments for this deadly disease. This review is complementary to earlier reviews and covers more recent reports of naturally occurring compounds, and in some cases synthetic analogs, largely from plants, fungi and marine organisms that demonstrate significant activity in the in vitro bioassays against Mycobacterium tuberculosis, and other mycobacterial species. Included also are traditional medicinal uses of specific plants when utilized to treat tuberculosis and other pulmonary diseases.

Antiplasmodial activity of extracts and quassinoids isolated from seedlings of Ailanthus altissima (Simaroubaceae).

Extracts and isolated compounds from seedlings of Ailanthus altissima, were assessed for antiplasmodial activity in vitro. Two quassinoids, ailanthone and 6alpha-tigloyloxychaparrinone, isolated from the active extracts showed activity against both chloroquine-resistant and chloroquine-sensitive strains of Plasmodium falciparum in vitro. Only ailanthone demonstrated low toxicity against the Vero cell line (kidney cells from the African green monkey). This is the first report of the isolation and antiplasmodial activity of 6alpha-tigloyloxychaparrinone from this species.

Geographic distribution of three alkaloid chemotypes of Croton lechleri.

Three known alkaloids, isoboldine (2), norisoboldine (1), and magnoflorine (8), have been isolated for the first time from Croton lechleri, a source of the wound healing latex "sangre de grado". An HPLC system was developed, and a large number of latex and leaf samples of C. lechleri from 22 sites in northern Peru and Ecuador were analyzed to gain an understanding of the natural variation in alkaloid content for the species. Up to six alkaloids were found to occur in the leaves including, in addition to those listed above, thaliporphine (3), glaucine (4), and taspine (9), whereas the latex contained only 9. Taspine (9) is the component that has been previously found to be responsible for the wound healing activity of C. lechleri latex, and its mean concentration throughout the range examined was found to be 9% of the latex by dry weight. In addition, three chemotypes are defined based on the alkaloid content of the leaves, and the geographic distribution of these chemotypes is discussed along with a quantitative analysis of the alkaloid content as a function of chemotype.

PHYLOGENETIC IMPLICATIONS OF DIVERSE SEED TYPES, CHROMOSOME NUMBERS, AND POLLEN MORPHOLOGY IN HOUSTONIA (RUBIACEAE).

Seed and pollen morphology were studied by light microscopy and scanning electron microscopy in 39 North and Central American species of Houstonia (including Hedyotis, but excluding Oldenlandia). Chromosome counts were obtained for eight taxa, of which five lacked previous chromosome data. A chromosome number of n = 17 for Houstonia gracilis is a new base number for the genus. Seed external morphology in the genus is very diverse, including variation in compression, margins, testa surfaces, and elaboration of ventral cavities or depressions and hilar ridges or their absence. Three types of pollen apertures are recognized: colporate with type A os, colpororate, and colporate with type B os, the last the most advanced type, occurring in H. caerulea and related species. The 39 species are arranged in twelve groups, based on correlation of seed, pollen, and chromosome data. Geographic distribution provides supplementary evidence for the distinctness and integrity of the six principal groups each composed of 2-9 species. Five of the six minor groups each with one species need chromosome data to facilitate future taxonomic decisions. Chromosome numbers of x = 6, 7, 8, 9, 10, 11, 13, and 17 are now known in this genus, and phylogenetic implications of the combined data are discussed.