Molecular orbital and topological electron density study of n → π* interactions: amides and thioamides cases.

The n → π* interactions were studied in amides and thioamides systems models, through the analysis of the electron density topology along with the Natural Bonding Orbital (NBO) approach. The effect of the dispersion terms was assessed using different DFT functionals. The NBO, independent gradient model (IGM), and the analysis of the reduced density gradient outcomes show that dispersion forces play a significant role in the strength of n → π* interactions. The IGM results indicate that δg height values for n → π* interactions do not extend beyond 0.025. All the methods used in this work predict that n → π* interaction between pairs of thioamides is stronger than those between amides. However, the electron density topology-based methods were not able to replicate the trends in the relative force of this interaction found in the experimental and NBO results.

Effect of extracts from several sponges of Yucatan Coast on Giardia lamblia and preliminary chemical investigation of the bioactive extract of Haliclona (Reinera) tubifera.

In this study, twenty-four organic extracts from six marine sponge species, collected at shallows of Yucatan, Mexico, were evaluated against Giardia lamblia trophozoites and Vero cells. The dichloromethane and hexane extracts of Haliclona tubifera exhibited the highest antigiardiasic activity (IC50 = 1.00 and 2.11 µg/mL, respectively), as well as high selectivity (SI = 41.8 and > 47.4, respectively), while ethyl acetate and methanol extracts of Cinachyrella alloclada, and methanol extract of Suberites aurantiaca showed moderate activity. Contrastingly, the extracts of Halichondria magniculosa and Oceanapia nodosa were considered non actives. Consequently, the dichloromethane extract of H. tubifera were subject to an exploratory chemical study, isolating cholesterol, two benzaldehyde derivatives, three benzoic acid derivatives, cytosine, and thymine.

Microwave-enhanced synthesis of 26-amino-22-oxocholestanes and their cytotoxic activity.

The synthesis of a series of 26-amino-22-oxocholestanes derived from diosgenin was accomplished via the substitution of an iodine atom at C-26 by primary and secondary amines. The reactions were conducted in refluxing acetonitrile and through microwave-assisted heating. The latter shows significant improvements in terms of reaction times going from hours to a few minutes or even seconds for completion. Only one of the selected amines, 4-aminourazole, did not yield the substitution product and the imine formation pathway was investigated instead, achieving the 26-iminourazole-22-oxocholestane. All the final products have been characterized and the cytotoxic activity of three of them has been evaluated in SiHa, MCF-7 and MDA tumor cell lines by the sulforhodamine B assay.

Cytotoxic and antiproliferative activity of thiazole derivatives of Ochraceolide A.

A series of 15 novel 1,3-thiazole amide derivatives of the pentacyclic triterpene Ochraceolide A (1) was synthesized, characterized, and evaluated in vitro against three human cancer cell lines (MCF-7, MDA-MB-231 and SiHa) and a normal cell line (Vero). Synthetic derivatives were obtained by acylation of the 2-aminothiazole triterpene 2, previously reported. Remarkably, the 5-nitrofuramide derivative (2o) showed better cytotoxic and antiproliferative activity than compound 2 and the other derivatives against the three cancer cell lines with CC50 and IC50 values of 1.6-12.7 µM. Furthermore, butyramide derivative (2c) was approximately 25 times more selective than 2, as well as 3.4 times more selective than Docetaxel, against SiHa cells in the cytotoxic assay, while the phenyl amide derivatives were inactive against the three cancer cell lines.

Cytotoxic activity against breast cancer cells of two species of marine sponges from shallows of Yucatan peninsula.

This study aimed to evaluate the in vitro activity of extracts of two marine sponge species, occurring in the shallows of the Yucatan peninsula coast, on two cancer and one normal mammalian cell lines. Hexane, dichloromethane, ethyl acetate and methanol extracts of Halichondria magniconulosa and Halichondria melanadocia were screened for their cytotoxic activity against hormone-dependent breast cancer (MCF-7) and human cervix cancer (SiHa) cell lines. The ethyl acetate extract of H. magniconulosa exhibited significant cytotoxicity against MCF-7 cells to a CC50 of 0.8 µg/mL, as well as high selectivity (SI = 24.5). On the other hand, SiHa cells were moderately sensitive to the dichloromethane and ethyl acetate extracts of the same species. (CC50 = 34.9 and 31.5 µg/mL, respectively). None of the extracts of H. melanadocia were considered active due their CC50's were ranged from 59.0 to 94.5 µg/mL.

Trichomonicidal activity of a new anthraquinone isolated from the roots of Morinda panamensis Seem.

Trichomoniasis, caused by the protozoan parasite Trichomonas vaginalis, is the most common nonviral sexually transmitted infection worldwide. Although drug treatment is available, unpleasant side effects and increased resistance to the nitroimidazole family have been documented. Hence, there is a need for the identification of new and safe therapeutic agents against T. vaginalis. Antimicrobial activity of anthraquinone compounds has been reported by a number of authors. The genus Morinda is well known for the diversity of anthraquinones with numerous biological activities. A new anthraquinone, lucidin-ω-isopropyl ether, was isolated from the roots of Morinda panamensis Seem. The structure of the compound was determined by 1 H and 13 C Nuclear Magnetic Resonance (NMR) analyses, in addition to comparison with literature reports. Using in vitro susceptibility assay, the half inhibitory concentration (IC50 ) of lucidin-ω-isopropyl ether for T. vaginalis (1.32 µg/mL) was found similar to that of metronidazole concentration tested (6 µM = 1.03 µg/mL). In addition, this anthraquinone was capable of inhibiting the parasite's ability to kill HeLa cells and decreased proteolytic activity of the proteinase TvMP50 from T. vaginalis. This was associated with the decreased expression of the mp50 gene. These results demonstrate the trichomonicidal potential by lucidin-ω-isopropyl ether. Further action-mode studies are necessary to elucidate the antiparasitic mechanism of this new anthraquinone to develop a more potent antitrichomonal agent.

Crystal structure of ochraceolide A isolated from Elaeodendron trichotomum (Turcz.) Lundell.

The title compound, C30H44O3 [systematic name: 6aR,6 bR,8aS,9aR,12aR,14bR)-4,4,6a,6;b,8a,14b-hexa-methyl-12-methyl-eneicosa-hydro-3H-phenanthro[1',2':6,7]indeno-[2,1-b]furan-3,11(2H)-dione], is a triterpene lactone, which was isolated from di-chloro-methane extract of Elaeodendron trichotomum (Turcz.) Lundell (celastraceae) stem bark. The compound has a lupane skeleton and consists of four fused six-membered rings and two five-membered rings. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds into a three-dimensional network. The configuration of ochraceolide A was proposed based on analogue compounds which belong to the lupane type.

Development of newly sanguinarine biosynthetic capacity in in vitro rootless shoots of Argemone mexicana L. Mexican prickly poppy.

OBJECTIVE: To analyze berberine and sanguinarine biosynthetic capacities of both in vitro shoot and root cultures of Argemone mexicana and tissues from entire plants at different developmental stages. RESULTS: Berberine and sanguinarine were equally distributed in roots and aerial tissues of developing plantlet whereas, in juvenile plants, sanguinarine was only detected in roots. This alkaloid distribution was consistent with that of biosynthetic transcripts in juvenile plants. However, lower transcript abundance in plantlets´ leaves suggests that alkaloids were mainly formed in roots and then mobilized to this tissue. In vitro root cultures maintained similar alkaloid profiles to those from intact seedlings and plantlets. However, in addition to berberine, rootless shoot cultures accumulated high levels of sanguinarine and biosynthetic transcripts. CONCLUSION: In vitro shoot cultures of A. mexicana can synthesize sanguinarine in addition to berberine. This represent a convenient system for the production of both alkaloids.

ANTIPROTOZOAL ACTIVITY OF EXTRACTS OF ELAEODENDRON TRICHOTOMUM (CELASTRACEAE).

BACKGROUND: Chagas disease, amebiasis, giardiasis and trichomoniasis represent a serious health problem in Latin America. The drugs employed to treat these illnesses produce important side effects and resistant strains have appeared. The present study was aimed to evaluate the antiprotozoal activity of leaves, stem bark and root bark of Elaeodendron trichotomum, a celastraceus, that is used in Mexico as an anti-infective in febrile-type diseases. MATERIALS AND METHODS: Dichloromethane and methanol extracts of leaves, bark and roots of Elaeodendron trichotomum were tested against Entamoeba histolytica, Giardia lamblia, Trichomonas vaginalis, and Trypanosoma cruzi. A quantitative HPLC analysis of pristimerin and tingenone was performed. RESULTS: The dichloromethane extract of roots was active against E. histolytica, G. lamblia, T. vaginalis, and T. cruzi, at IC50's of 0.80, 0.44, 0.46, and 2.68 µg/mL, respectively. The HPLC analysis revealed the presence of tingenone (3.84%) and pristimerin (0.14%). CONCLUSIONS: The dichloromethane extract of the roots bark showed significant activity against all screened protozoa.

Resin glycosides from Ipomoea tyrianthina and their sedative and vasorelaxant effects.

The methanol-soluble extract from the root of Ipomoea tyrianthina was studied in order to isolate compounds with activity on the central nervous system and vasorelaxant effects. Chromatographic methods were used to isolate and purify seven new glycolipids (2-8). The structures of compounds 1-8 were elucidated by a combination of NMR spectroscopy and mass spectrometry. Tyrianthinoic acid (1) is a glycosidic acid composed of a linear pentasaccharide core bonded to a 11-hydroxyhexadecanoic acid. The structure of tyrianthinic acids III (2), IV (3), and V (4) consists of a partially acylated tyrianthinoic acid. Tyrianthinic acid VI (8) is a tetrasaccharide core bonded to a jalapinolic acid, acylated by a 2-methyl-3-hydroxybutanoic acid. Tyrianthins C (5), D (6), and E (7) are ester-type heterodimers of scammonic acid A with different acylating residues in the two monomeric units. The macrolactonization site was located at C-3 of the rhamnose unit. The position of the ester linkage for monomeric unit B on the macrocyclic unit A was established at C-4 of the terminal quinovose. Compounds 5-7 increased the sleeping time induced by pentobarbital and the release of gamma-aminobutyric acid in brain cortex. In addition, compounds 5-7 showed significant in vitro relaxant effects on aortic rat rings, in endothelium- and concentration-dependent manners.

Cytotoxic diterpenes from roots of Crossopetalum gaumeri, a Celastraceae species from Yucatan Peninsula.

Four new diterpenes, crossogumerins A-D (1-4) along with six known ones (5-10) were isolated from the root bark of Crossopetalum gaumeri, an endemic medicinal plant from the Yucatan Peninsula. Their structures were elucidated on the basis of 1D and 2D NMR techniques, including HMQC, HMBC, and ROESY experiments. Compounds 1-5, 8-10 were evaluated for cytotoxicity against HeLa (carcinoma of the cervix) and Hep-2 (lung carcinoma) human tumor cells lines and against normal Vero cells (African green monkey kidney) in lag and log phase of growth. Podocarpane diterpenes, crossogumerin B (2) and nimbiol (10), exhibited the highest activity against HeLa cells (IC50 values of 3.1 and 8.1 µM, respectively), but also selectivity on Vero cells (SI 22.6 and 7.5, respectively). The preliminary SAR studies suggest that an epoxy moiety in ring B and a hydrogen bond-donor group strategically positioned in the diterpene core are important requirements for cytotoxicity and selectivity.

4-Methyl-N-(4-methyl-phenyl-sulfon-yl)-N-[4-(4-methyl-phen-yl)-1,3-thia-zol-2-yl]benzene-sulfonamide.

There are two independent mol-ecules in the asymmetric unit of the title compound, C24H22N2O4S3. In each, the sulfonamide N atoms reveal nearly a trigonal-planar geometry with two S atoms of the O=S=O groups and one C atom of the thia-zole ring; the angles around the N atoms are between 117.00 (13) and 123.86 (9)°. The methyl-phenyl-sulfonyl groups are in anti conformations, forming dihedral angles of 78.00 (7)/72.53 (5) and 77.09 (6)/71.50 (7)° with the trigonal S-N-S planes in the two mol-ecules. The thia-zole groups are rotated around the C-N bonds and are almost perpendicular to the S-N-S plane [dihedral angles of 78.00 (7)/72.53 (5) and 77.09 (6)/71.50 (7)°]. In the crystal, pairs of C-H⋯O inter-actions, with the O atoms of the sulfonamide groups as acceptors, link each of the independent mol-ecules into inversion dimers.

Dihydrospinochalcone-a and epi-flemistrictin-B, natural isocordoin derivatives from the root extract of Lonchocarpus xuul.

Purification of the root extract of Lonchocarpus xuul resulted in the isolation and identification of dihydrospinochalcone A (1) and epi-flemistrictin B (2) as additional natural isocordoin derivatives. Identification was based on the analysis of their spectroscopic data and by comparing these with those of previously reported metabolites.

Design, synthesis, and in vitro antiprotozoal, antimycobacterial activities of N-{2-[(7-chloroquinolin-4-yl)amino]ethyl}ureas.

We have synthesized a new series of quinoline tripartite hybrids from chloroquine, ethambutol, and isoxyl drugs, using a short synthetic route. Compounds 1-8 were tested in vitro against five protozoa (Giardia intestinalis, Trichomonas vaginalis,Entamoeba histolytica, Leishmania mexicana and Trypanosoma cruzi) and Mycobacterium tuberculosis. N-(4-Butoxyphenyl)-N'-{2-[(7-chloroquinolin-4-yl)amino]ethyl}urea (6) was the most active compound against all parasites tested. Compound 6 was 670 times more active than metronidazole, against G. intestinalis. It was as active as pentamidine against L. mexicana, and it was twofold more potent than ethambutol and isoxyl versus M. tuberculosis. This compound could be considered as a new broad spectrum antimicrobial agent.

Glycolipid ester-type heterodimers from Ipomoea tyrianthina and their pharmacological activity.

Tyrianthins A (1) and B (2), two new partially acylated glycolipid ester-type heterodimers were isolated from Ipomoea tyrianthina. Scammonic acid A was determined as the glycosidic acid in both monomeric units. Tyrianthin A (1) (IC(50) 0.24+/-0.09 microM and E(max) 81.80+/-0.98%), and tyrianthin B (2) (IC(50) 0.14+/-0.08 microM and E(max) 87.68+/-0.72%) showed significant in vitro relaxant effect on aortic rat rings, in endothelium- and concentration-dependent manners. Also, these compounds were able to increase the release of GABA and glutamic acid in brain cortex, and displayed weak antimycobacterial activity.

Tyrianthinic acids from Ipomoea tyrianthina and their antimycobacterial activity, cytotoxicity, and effects on the central nervous system.

Four new partially acylated tetrasaccharides of 11-hydroxyhexadecanoic acid (1-4) were isolated from a methanolic extract of Ipomoea tyrianthina. The structures of these compounds were elucidated by spectroscopic and chemical methods. The resin glycoside composition of I. tyrianthina varied with the location of growth in Mexico. Compounds 1-4 showed antimycobacterial activity, were cytotoxic against the KB cell line, and, in a mouse model, exhibited potentiation of hypnosis induced by pentobarbital, protected against seizures induced by pentylenetetrazole, and released GABA and glutamic acid.

Resin glycosides from the roots of Ipomoea tyrianthina and their biological activity.

Seven new tetrasaccharide glycosides, tyrianthins 1-7 (1-7), along with six known glycolipids were isolated from the roots of Ipomoea tyrianthina, and their structures were elucidated by spectroscopic and chemical methods. The content of resin glycosides in samples collected in three different regions was analyzed and compared, and the results showed that the flowering or dry season did not have any effect on the chemical composition for the same locality, but the growing location itself did affect the chemical composition of resin glycosides. Intraperitoneal administration to mice of tyrianthin 6 (6) resulted in antidepressant activity. Tyrianthin 6 (6), scammonin 1 (8), and scammonin 2 (9) exhibited dose-dependent protective effects against pentylenetetrazole-induced seizures. Also, tyrianthin 6 (6) and scammonin 2 (9) produced relaxant effects on spontaneous contractions in the isolated rat ileum.