Molecules2014, 19(4), 5448-5458; doi:10.3390/molecules19045448 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: Using a bioassay-directed chromatographic separation, two ellagic acids were obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis L.On the basis of chemical and spectroscopic methods, the two ellagic acids were identified as 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside and 3,3',4-tri-O-methylellagic acid. Stimulation of cell proliferation was assayed in hematopoietic progenitor cells using the Cell Counting kit-8 method. The megakaryocyte differentiation was determined in human erythroleukemia (HEL) cells using Giemsa staining and flow cytometry analysis. The ellagic acids significantly stimulated the proliferation of Baf3/Mpl cells. Morphology analysis and megakaryocyte specific-marker CD41 staining confirmed that the ellagic acids induced megakaryocyte differentiation in HEL cells. This is the first time that 3,3',4-tri-O-methylellagic acid or 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside are reported to induce megakaryopoiesis, suggesting a class of small molecules which differ from others non-peptidyl, and appears to have potential for clinical development as a therapeutic agent for patients with blood platelet disorders.
Molecules2014, 19(4), 5434-5447; doi:10.3390/molecules19045434 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: This paper presents the quantification, antioxidant and antimicrobial activity of capsaicin, dihydrocapsaicin and the flavonoid chrysoeriol isolated from different extracts (hexane and acetonitrile extracts from whole fruit, peel and seed) of Capsicum frutescens (pimenta malagueta). The acetonitrile extract of the seeds, peel and whole fruits contained capsaicin as a major component, followed in abundance by dihydrocapsaicin and chrysoeriol. The antimicrobial activity of the isolated compounds against seven microorganisms showed chrysoeriol was the most active compound. In the antioxidant test, the acetonitrile extract from the whole fruit showed the highest activity. The antioxidant activity of pimenta malagueta may be correlated with its phenolic content, principally with the most active compound, capsaicin.
Molecules2014, 19(4), 5421-5433; doi:10.3390/molecules19045421 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: The aerial parts of Ipomoea batatas are described herein to produce four new resin glycosides, designated as ipomotaosides A, B, C, and D. Ipomotaoside A was found to present inhibitory activity on both cyclooxygenases. However, the conformational elucidation of these molecules may be difficult due to their high flexibility. In this context, the current work presents a conformational characterization of ipomotaosides A–D in aqueous and nonaqueous solvents. The employed protocol includes metadynamics evaluation and unrestrained molecular dynamics simulations (MD). The obtained data provided structural models for the ipomotaosides in good agreement with previous ROESY distances measured in pyridine. Accordingly, the most abundant conformation of ipomotaoside A in solution was employed in flexible docking studies, providing a structural basis for the compound’s inhibition of COX enzymes. The so-obtained complex supports resin glycosides’ role as original scaffolds for future studies, aiming at structural optimization and development of potential new anti-inflammatory agents.
Molecules2014, 19(4), 5402-5420; doi:10.3390/molecules19045402 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1–C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1–C9 and also the free ligands L1–L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10−6 mol mL−1 to 10−8 mol mL−1) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the complexes are not as toxic (IC50 values are much higher—30 to 200 fold—than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs).
Molecules2014, 19(4), 5379-5401; doi:10.3390/molecules19045379 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: MicroRNAs (miRNA) are small, non-coding, RNAs with gene expression regulator roles. As an important class of regulators of many cellular pathways, miRNAs are involved in many signaling pathways and DNA damage repair processes, affecting cellular radiosensitivity. Their role has led to interest in oncological implications to improve treatment results. MiRNAs represent a great opportunity to enhance the efficacy of radiotherapy treatments—they can be used to profile the radioresistance of tumors before radiotherapy, monitor their response throughout the treatment, thus helping to select intensification strategies, and also to define the final response to therapy along with risks of recurrence or metastatization. Even though many interesting studies support such potential, nowadays most studies on patient data are limited to experiments profiling tumor aggressiveness and response to radiotherapy. Moreover many studies report different although not conflicting results on the miRNAs evaluated for each tumor type. Without doubt, the clinical potential of such molecules for radiotherapy is striking and of high interest.
Molecules2014, 19(4), 5360-5378; doi:10.3390/molecules19045360 (doi registration under processing) - published online 24 April 2014 Show/Hide Abstract
Abstract: Neglected agricultural products (NAPs) are defined as discarded material in agricultural production. Corn cobs are a major waste of agriculture maize. Here, a methanolic extract from corn cobs (MEC) was obtained. MEC contains phenolic compounds, protein, carbohydrates (1.4:0.001:0.001). We evaluated the in vitro and in vivo antioxidant potential of MEC. Furthermore, its antiproliferative property against tumor cells was assessed through MTT assays and proteins related to apoptosis in tumor cells were examined by western blot. MEC showed no hydroxyl radical scavenger capacity, but it showed antioxidant activity in Total Antioxidant Capacity and DPPH scavenger ability assays. MEC showed higher Reducing Power than ascorbic acid and exhibited high Superoxide Scavenging activity. In tumor cell culture, MEC increased catalase, metallothionein and superoxide dismutase expression in accordance with the antioxidant tests. In vivo antioxidant test, MEC restored SOD and CAT, decreased malondialdehyde activities and showed high Trolox Equivalent Antioxidant Capacity in animals treated with CCl4. Furthermore, MEC decreased HeLa cells viability by apoptosis due an increase of Bax/Bcl-2 ratio, caspase 3 active. Protein kinase C expression increased was also detected in treated tumor cells. Thus, our findings pointed out the biotechnological potential of corn cobs as a source of molecules with pharmacological activity.