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This study aimed to analyze the combined impact of CO2 and drought stress at the flowering stage on carbon (C), nitrogen (N), and CN ratios in leaves, stem, and grains of bread wheat. Six diverse bread wheat genotypes, comprised of two commercial checks, two landraces, and two synthetics derivatives, were grown at two levels of CO2, i.e., 400 ppm and 800 ppm, and drought stress was imposed at the flowering stage through progressive soil drying. Stem, leaf, and grain samples were taken at maturity and concentrations of C and N were determined. Our results indicate that the threshold value of fraction of transpirable soil water (CFTSW) at which it diverges towards closure of stomata was different among genotypes and a higher range of values was estimated under elevated CO2. Drought significantly increased C levels in leaves and N levels in grains but decreased N levels in leaves, which increased CN ratios in leaves. In contrast, drought significantly reduced CN ratios in grains. Genotypes differed significantly in N content in grains, where the landrace derivative L2 maintained the highest N content. Moreover, pronounced changes in leaf N and CN ratios were induced by the combination of elevated CO2 and drought stress. Additionally, combined correlation and biplot analyses indicate a strong positive association of grain CN (GCN) with grain number, weight, and grain yield. These effects possibly interact with drought to strongly interfere with the impact of elevated CO2. The differential performance of the tested genotypes shows that selection of appropriate germplasm is essential to maintain agricultural production. [ABSTRACT FROM AUTHOR]

Coronarin E is a main diterpene ever isolated from Hedychium yunnanense. With the aim to enlarge its potential application, four butenolide derivatives (compounds 4a, 4b, 5a and 5b) were obtained from coronarin E via synthetic method, and their antibacterial effects were also evaluated. It is noteworthy that compounds 5a and 5b exhibited stronger antibacterial activities against most of the tested bacterial strains than ampicillin and kanamycin, two first- and second-line antimicrobials in clinical. For example, minimum inhibitory concentration (MIC) of 5a, 5b, ampicillin and kanamycin against Acinetobacter baumanii were 2, 1, 8 and 4 μg/mL, respectively, and MIC of the four compounds mentioned above against Klebsiella pneumonia were 1, 0.5, 16 and 4 μg/mL, respectively. The current studies not only enrich the structural diversity of diterpenes derived from Hedychium genus, but also provide potent candidates for the development of antibacterial medicines. [ABSTRACT FROM AUTHOR]

The improvement of cancer chemotherapy remains a major challenge, and thus new drugs are urgently required to develop new treatment regimes. Curcumin, a polyphenolic antioxidant derived from the rhizome of turmeric (Curcuma longa L.), has undergone extensive preclinical investigations and, thereby, displayed remarkable efficacy in vitro and in vivo against cancer and other disorders. However, pharmacological limitations of curcumin stimulated the synthesis of numerous novel curcumin analogs, which need to be evaluated for their therapeutic potential. In the present study, we calculated the binding affinities of 50 curcumin derivatives to known cancer-related target proteins of curcumin, i.e., epidermal growth factor receptor (EGFR) and nuclear factor κB (NF-κB) by using a molecular docking approach. The binding energies for EGFR were in a range of −12.12 (±0.21) to −7.34 (±0.07) kcal/mol and those for NF-κB ranged from −12.97 (±0.47) to −6.24 (±0.06) kcal/mol, indicating similar binding affinities of the curcumin compounds for both target proteins. The predicted receptor-ligand binding constants for EGFR and curcumin derivatives were in a range of 0.00013 (±0.00006) to 3.45 (±0.10) µM and for NF-κB in a range of 0.0004 (±0.0003) to 10.05 (±4.03) µM, indicating that the receptor-ligand binding was more stable for EGFR than for NF-κB. Twenty out of 50 curcumin compounds showed binding energies to NF-κB smaller than −10 kcal/mol, while curcumin as a lead compound revealed free binding energies of >−10 kcal/mol. Comparable data were obtained for EGFR: 15 out of 50 curcumin compounds were bound to EGFR with free binding energies of <−10 kcal/mol, while the binding affinity of curcumin itself was >−10 kcal/mol. This indicates that the derivatization of curcumin may indeed be a promising strategy to improve targe specificity and to obtain more effective anticancer drug candidates. The in silico results have been exemplarily validated using microscale thermophoresis. The bioactivity has been further investigated by using resazurin cell viability assay, lactate dehydrogenase assay, flow cytometric measurement of reactive oxygen species, and annexin V/propidium iodide assay. In conclusion, molecular docking represents a valuable approach to facilitate and speed up the identification of novel targeted curcumin-based drugs to treat cancer. [ABSTRACT FROM AUTHOR]

The use of sunscreens is an established and recommended practice to protect skin from solar-induced damage. Around 30 UV filters can be used in sunscreen products in the European Union, which ought to follow the requirements of the regulation 1223/2009 to ensure their efficacy and safety for humans. Nevertheless, low photostability and putative toxicity for humans and environment have been reported for some UV filters. Particularly, the negative impact in marine organisms has recently raised concern on the scientific community. Therefore, it is important to develop new UV filters with improved safety profile and photostability. Over the last two decades, nearly 200 new compounds have revealed promising photoprotection properties. The explored compounds were obtained through different approaches, including exploration of natural sources, synthetic pathways, and nanotechnology. Almost 50 natural products and around 140 synthetic derivatives, such as benzimidazoles, benzotriazoles, hydroxycinnamic acids, xanthones, triazines, among others, have been studied aiming the discovery of novel, effective, and safer future photoprotective agents. Herein, we provide the reader with an overview about UV filters' challenges and prospects, offering a forward-looking to the next-generation of UV filters. [ABSTRACT FROM AUTHOR]

Cancer is the second most killer worldwide causing millions of people to lose their lives every year. In the case of women, breast cancer takes away the highest proportion of mortality rate than other cancers. Due to the mutation and resistance-building capacity of different breast cancer cell lines against conventional therapies, this death rate is on the verge of growth. New effective therapeutic compounds and treatment method is the best way to look out for in this critical time. For instance, new synthetic derivatives/ analogues synthesized from different compounds can be a ray of hope. Numerous synthetic compounds have been seen enhancing the apoptosis and autophagic pathway that directly exerts cytotoxicity towards different breast cancer cell lines. To cease the ever-growing resistance of multi-drug resistant cells against anti-breast cancer drugs (Doxorubicin, verapamil, tamoxifen) synthetic compounds may play a vital role by increasing effectivity, showing synergistic action. Many recent and previous studies have reported that synthetic derivatives hold potentials as an effective anti-breast cancer agent as they show great cytotoxicity towards cancer cells, thus can be used even vastly in the future in the field of breast cancer treatment. This review aims to identify the anti-breast cancer properties of several synthetic derivatives against different breast cancer and multi-drug-resistant breast cancer cell lines with their reported mechanism of action and effectivity. [ABSTRACT FROM AUTHOR]

Trichomonas vaginalis is an extracellular parasite that binds to the epithelium of the human urogenital tract and causes the sexually transmitted infection, trichomoniasis. In view of increased resistance to drugs belonging to the 5-nitroimidazole class, new treatment alternatives are urgently needed. In this study, eight semisynthetized triterpene derivatives were evaluated for in vitro anti-T. vaginalis activity. Ursolic acid and its derivative, 3-oxime-urs-12-en-28-oic-ursolic acid (9), presented the best anti-T. vaginalis activity when compared to other derivatives, with minimum inhibitory concentration (MIC) at 25 μM. Moreover, 9 was active against several T. vaginalis fresh clinical isolates. Hemolysis assay demonstrated that 9 presented a low hemolytic effect. Importantly, 25 μM 9 was not cytotoxic against the Vero cell lineage. Finally, we demonstrated that compound 9 acts synergistically with metronidazole against a T. vaginalis metronidazole-resistant isolate. This report reveals the high potential of the triterpenoid derivative 9 as trichomonicidal agent. [ABSTRACT FROM AUTHOR]

Esculetin, synonymous with 6,7-dihydroxycoumarin, is the main active ingredient of the traditional Chinese medicine Cortex Fraxini. The twig skin or trunk bark of Cortex Fraxini are used by herb doctors as a mild, bitter liver and gallbladder meridians’ nontoxic drug as well as dietary supplement. Recently, with a variety of novel esculetin derivatives being reported, the molecular mechanism research as well as clinical application of Cortex Fraxini and esculetin are becoming more attractive. This mini-review will consolidate what is known about the biological activities, the mechanism of esculetin and its synthetic derivatives over the past decade in addition to providing a brief synopsis of the properties of esculetin. [ABSTRACT FROM AUTHOR]

Chagas disease, caused by Trypanosoma cruzi, affects six to seven million people worldwide. Treatment is based on benznidazole, producing several side effects and debatable efficacy, highlighting the need for new alternative drugs. We investigated the activity of four C-4 functionalized azlactone derivatives (EPA-27, EPA-35, EPA-63 and EPA-91) as potential T. cruzi inhibitors. Screening with epimastigotes indicated EPA-35 as the best compound (IC50/24 h: 33 µM). This compound was 14.1 times more potent against intracellular amastigotes (IC50/24 h: 2.34 µM). Treatment of infected Vero cells for 72 h (up to 30 µM EPA-35) resulted in a dose-dependent decrease in number of trypomastigotes and amastigotes released in the supernatant, but the amastigote/trypomastigote ratio remained constant, indicating that amastigote growth was disturbed, but cell differentiation was unaffected. Analysis of treated epimastigotes by flow cytometry indicated that the plasma membrane remained intact, but there was a significant decrease in mitochondrial membrane potential. The pattern of cell distribution in the cell cycle stages (G1, G2, M) was unaltered in treated epimastigotes, indicating a trypanocidal rather than a trypanostatic activity. Scanning electron microscopy and flow cytometry showed epimastigotes with a round shape and decrease in cell size. Taken together, our data indicate that the EPA-35 is effective against T. cruzi. Synthetic transformation of EPA-35 into other derivatives may provide promising compounds for further evaluation against this parasite. [ABSTRACT FROM AUTHOR]

Although considerable effort and progress has been made in the search for new anticancer drugs and treatments in the last several decades, cancer remains a major public health problem and one of the major causes of death worldwide. Many sources, including plants, animals, and minerals, are of interest in cancer research because of the possibility of identifying novel molecular therapeutics. Moreover, structure-activity-relationship (SAR) investigations have become a common way to develop naturally derived or semi-synthetic molecular analogues with improved efficacy and decreased toxicity. In 2012, approximately 138 molecules from marine sources, including isolated compounds and their associated analogues, were shown to be promising anticancer drugs. Among these, 62% are novel compounds. In this report, we review the marine compounds identified in 2012 that may serve as novel anticancer drugs. [ABSTRACT FROM AUTHOR]

Seven (-)-arct igenin derivat ives 1-7 were designed and synthesized by using Mannich and acylat ion methods to improve the act ivity and bioavailability of (-)-arct igenin. St ructures of compounds 1-7 were elucidated on the basis of spectroscopic analysis and chemical evidence. Ant icancer activity of these compounds on SGC7901 was assayed in vitro. [ABSTRACT FROM AUTHOR]

( − )-Arctigenin, an important active constituent of the traditional Chinese herb Fructus Arctii, was found to exhibit various bioactivities, so it can be used as a good lead compound for further structure modification in order to find a safer and more potent medicine. ( − )-Arctigenin derivatives1–5of ( − )-arctingen were obtained by modifying with ammonolysis at the lactone ring and sulphonylation at C (6′) and C (6″) andO-demethylation at CH3O-C (3′), CH3O-C (3″) and CH3O-C (4″), and their anticancer bioactivities were examined. [ABSTRACT FROM PUBLISHER]

7,8-Dihydroxyflavone (7,8-DHF) acts as a TrkB receptor-specific agonist. It mimics the physiological actions of brain-derived neurotrophic factor (BDNF) and demonstrates remarkable therapeutic efficacy in animal models of various neurological diseases. Nonetheless, its in vivo pharmacokinetic profiles and metabolism remain unclear. Here we report that 7,8-DHF and its O-methylated metabolites distribute in mouse brain after oral administration. Both hydroxy groups can be mono-methylated, and the mono-methylated metabolites activate TrkB in vitro and in vivo. Blocking methylation, using COMT inhibitors, diminishes the agonistic effect of TrkB activation by 7,8-DHF or 4′-dimethylamino-7,8-DHF, supporting the contribution of the methylated metabolite to TrkB activation in mouse brain. Moreover, we have synthesized several methylated metabolite derivatives, and they also potently activate the TrkB receptor and reduce immobility in both forced swim test and tail suspension test, indicating that these methylated metabolites may possess antidepressant activity. Hence, our data demonstrate that 7,8-DHF is orally bioavailable and can penetrate the brain-blood barrier. The O-methylated metabolites are implicated in TrkB receptor activation in the brain. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Cancer continues to be a major public health problem despite the efforts that have been made in the search for novel drugs and treatments. The current sources sought for the discovery of new molecules are plants, animals and minerals. During the past decade, the search for anticancer agents of marine origin to fight chemo-resistance has increased greatly. Each year, several novel anticancer molecules are isolated from marine organisms and represent a renewed hope for cancer therapy. The study of structure-function relationships has allowed synthesis of analogues with increased efficacy and less toxicity. In this report, we aim to review 42 compounds of marine origin and their derivatives that were published in 2011 as promising anticancer compounds. [ABSTRACT FROM AUTHOR]

The natural dibenzylbutyrolactone type lignanolide (–)-arctigenin, which was prepared from fructus arctii, showed obvious anticancer activity. The synthesis of four new (–)-arctigenin derivatives and their anticancer bioactivities were examined. The structures of the four new synthetic derivatives were elucidated. [ABSTRACT FROM PUBLISHER]

Although considerable progress in oncology therapeutics has been achieved in the last century, cancer remains one of major death causes in the World and for this reason, the development of novel cancer drugs remains a pressing need. Natural marine compounds represent an interesting source of novel leads with potent chemotherapeutic or chemo-preventive activities. In the last decades, structure-activity-relationship studies have led to the development of naturally-derived or semi-synthetic analogues with improved bioactivity, a simplified synthetic target or less toxicity. We aim here to review a selection of natural compounds with reported anticancer activity isolated of marine sources and their associated analogues published in 2010. [ABSTRACT FROM AUTHOR]

Ribosomally synthesized natural antimicrobial peptides (AP) and their synthetic derivatives are small, cationic, amphipathic molecules of 12–50 amino acids with unusually broad activity spectra. These peptides kill microorganisms by a common mechanism, which involves binding to the lipid bilayer of biological membranes, forming pores, and ultimately followed by cell lysis. Several AP from mammals, amphibians, insects, plants and their synthetic derivatives demonstrate promising in vitro activity against various pathogenic fungi including azole-resistant Candida albicans strains. In addition to their antimicrobial activity, some AP such as lactoferrin, interact with a variety of host cells and can increase the activity of natural killer and lymphokine activated killer cells. Pretreatment of polymorphonuclear neutrophil leukocytes (PMN) or monocytes with these AP also may upregulate superoxide release. AP as potential new antifungal agents offer some advantages, such as rapid killing of pathogenic fungi and the difficulty to raise mutants resistant to these peptides. AP are limited by their nonselective toxicity, stability, immunogenicity and their costs of production. Potential clinical applications of AP in the future have to be further explored in preclinical and clinical studies to assess their impact as a new class of antifungals. [ABSTRACT FROM AUTHOR]

Melanosis is an unsolved problem of the crustacean industry and the cause of great loss of value. This study investigates the effect of two potent, natural antioxidants isolated from olive waste (hydroxytyrosol, HT and 3,4-dihydroxyphenylglycol, DHPG) and three novel HT-derivatives containing selenium and sulfur (dihydroxytyrosyl diselenide, N-hydroxytyrosyl selenourea, and N-hydroxytyrosyl thiourea) on the prevention of melanosis in Atlantic ditch shrimp (Palaemonetes varians) during refrigerated storage. These results clearly demonstrate the positive inhibitory effect of DHPG and dihydroxytyrosyl diselenide on delaying melanosis in vivo, although this effect was not dose dependent. The effect was associated with a concomitant-inhibitory effect on tyrosinase activity in vitro. To our knowledge, so far no studies on the prevention of melanosis have been conducted on this small specie of shrimp which is available in large quantities at any time of the year at low cost. Studies with these promising compounds could then be extended to other more economically important species with a greater guarantee of success. [ABSTRACT FROM AUTHOR]

Piplartine (1) is an alkamide extracted from plants of the genus Piper which shows several pharmacological properties, including antitumor activity. To improve this activity, a series of analogues based on 1 have been synthesized by esterification and amidation using the 3,4,5-trimethoxycinnamic acid-like starting material. During the study, the moieties 3-(3,4,5-trimethoxyphenyl)acrylate and 3-(3,4,5-trimethoxyphenyl)acrylamide were maintained on esters and amides respectively. Meanwhile, functional changes were exploited, and it was revealed that the presence of two aromatic rings in the side-chain was important to improve the cytotoxic activity against the U87MG cell line, such as the compound (E)-benzhydryl 3-(3,4,5-trimethoxyphenyl)acrylate (10), an ester that exhibited strong cytotoxicity and a similar level of potency to that of paclitaxel, a positive control. Compound 10 had a marked concentration-dependent inhibitory effect on the viability of the U87MG cell line with apoptotic and oxidative processes, showing good potential for altering main molecular pathways to prevent tumor development. Moreover, it has strong bioavailability with non-genotoxic and non-cytotoxic properties on human blood cells. In conclusion, the findings of the present study demonstrated that compound 10 is a promising agent that may find applications combatting diseases associated with oxidative stress and as a prototype for the development of novel drugs used in the treatment of glioblastoma. [ABSTRACT FROM AUTHOR]