Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry最新文献

{"title":"Doxorubicin Conjugated to Glutathione Stabilized Gold Nanoparticles (Au-GSH-Dox) as an Effective Therapeutic Agent for Feline Injection-Site Sarcomas—Chick Embryo Chorioallantoic Membrane Study","authors":"K. Zabielska-Koczywąs, I. Dolka, M. Król, A. Żbikowski, W. Lewandowski, J. Mieczkowski, M. Wójcik, R. Lechowski","doi":"10.3390/molecules22020253","DOIUrl":"https://doi.org/10.3390/molecules22020253","url":null,"abstract":"Feline injection-site sarcomas are malignant skin tumours with a high local recurrence rate, ranging from 14% to 28%. The treatment of feline injection-site sarcomas includes radical surgery, radiotherapy and/or chemotherapy. In our previous study it has been demonstrated that doxorubicin conjugated to glutathione-stabilized gold nanoparticles (Au-GSH-Dox) has higher cytotoxic effects than free doxorubicin for feline fibrosarcoma cell lines with high glycoprotein P activity (FFS1, FFS3). The aim of the present study was to assess the effectiveness of intratumoural injection of Au-GSH-Dox on the growth of tumours from the FFS1 and FFS3 cell lines on chick embryo chorioallantoic membrane. This model has been utilized both in human and veterinary medicine for preclinical oncological studies. The influence of intratumoural injections of Au-GSH-Dox, glutathione-stabilized gold nanoparticles and doxorubicin alone on the Ki-67 proliferation marker was also checked. We demonstrated that the volume ratio of tumours from the FFS1 and FFS3 cell lines was significantly (p < 0.01) decreased after a single intratumoural injection of Au-GSH-Dox, which confirms the positive results of in vitro studies and indicates that Au-GSH-Dox may be a potent new therapeutic agent for feline injection-site sarcomas.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77628254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biologic Stress, Oxidative Stress, and Resistance to Drugs: What Is Hidden Behind","authors":"M. Pantelidou, K. Tsiakitzis, E. Rekka, P. Kourounakis","doi":"10.3390/molecules22020307","DOIUrl":"https://doi.org/10.3390/molecules22020307","url":null,"abstract":"Stress can be defined as the homeostatic, nonspecific defensive response of the organism to challenges. It is expressed by morphological, biochemical, and functional changes. In this review, we present biological and oxidative stress, as well as their interrelation. In addition to the mediation in biologic stress (central nervous, immune, and hormonal systems) and oxidative stress, the effect of these phenomena on xenobiotic metabolism and drug response is also examined. It is concluded that stress decreases drug response, a result which seems to be mainly attributed to the induction of hepatic drug metabolizing enzymes. A number of mechanisms are presented. Structure-activity studies are also discussed. Vitamin E, as well as two synthetic novel compounds, seem to reduce both oxidative and biological stress and, consequently, influence drug response and metabolism.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"33 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89865292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Essential Oil of Monarda didyma L. (Lamiaceae) Exerts Phytotoxic Activity In Vitro against Various Weed Seeds","authors":"D. Ricci, F. Epifano, D. Fraternale","doi":"10.3390/molecules22020222","DOIUrl":"https://doi.org/10.3390/molecules22020222","url":null,"abstract":"The chemical composition of the essential oil of the flowering aerial parts of Monarda didyma L. cultivated in central Italy was analyzed by Gas Chromatography/Mass Spectrometry (GC/MS). The major compounds of the oil were thymol (59.3%), p-cymene (10.3%), terpinolene (9.2%), δ-3-carene (4.4%), myrcene (3.7%), and camphene (3.4%). The essential oil was tested in vitro for its anti-germination activity against Papaver rhoeas L., Taraxacum officinale F. H. Wigg., Avena fatua L., Raphanus sativus L. and Lepidium sativum L. seeds, demonstrating good inhibitory activity in a dose-dependent way. The exposure of the employed weed seeds to M. didyma essential oil and thymol solution (59.3%) increased the level of hydrogen peroxide (H2O2) and malondialdehyde (MDA), markers of oxidative stress, in emerging 5-day-old rootlets.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"62 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90998227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porous Hydrogen-Bonded Organic Frameworks","authors":"Yi-fei Han, Ying-xue Yuan, Hong‐Bo Wang","doi":"10.3390/molecules22020266","DOIUrl":"https://doi.org/10.3390/molecules22020266","url":null,"abstract":"Ordered porous solid-state architectures constructed via non-covalent supramolecular self-assembly have attracted increasing interest due to their unique advantages and potential applications. Porous metal-coordination organic frameworks (MOFs) are generated by the assembly of metal coordination centers and organic linkers. Compared to MOFs, porous hydrogen-bonded organic frameworks (HOFs) are readily purified and recovered via simple recrystallization. However, due to lacking of sufficiently ability to orientate self-aggregation of building motifs in predictable manners, rational design and preparation of porous HOFs are still challenging. Herein, we summarize recent developments about porous HOFs and attempt to gain deeper insights into the design strategies of basic building motifs.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86115898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ent-Abietanoids Isolated from Isodon serra","authors":"J. Wan, Hua-Yi Jiang, Jian-Wei Tang, Xing-Ren Li, Xue Du, Yan Li, Han-Dong Sun, J. Pu","doi":"10.3390/molecules22020309","DOIUrl":"https://doi.org/10.3390/molecules22020309","url":null,"abstract":"Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1), xerophilusin XVII (2), and enanderianins Q and R (3 and 4), while the known ones were identified as rubescansin J (5), (3α,14β)-3,18-[(1-methylethane-1,1-diyl)dioxy]-ent-abieta-7,15(17)-diene-14,16-diol (6), xerophilusin XIV (7), and enanderianin P (8), respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 μM) and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480).","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90882360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wine Flavonoids in Health and Disease Prevention","authors":"I. Fernandes, Rosa Pérez-Gregorio, Susana Soares, N. Mateus, V. de Freitas","doi":"10.3390/molecules22020292","DOIUrl":"https://doi.org/10.3390/molecules22020292","url":null,"abstract":"Wine, and particularly red wine, is a beverage with a great chemical complexity that is in continuous evolution. Chemically, wine is a hydroalcoholic solution (~78% water) that comprises a wide variety of chemical components, including aldehydes, esters, ketones, lipids, minerals, organic acids, phenolics, soluble proteins, sugars and vitamins. Flavonoids constitute a major group of polyphenolic compounds which are directly associated with the organoleptic and health-promoting properties of red wine. However, due to the insufficient epidemiological and in vivo evidences on this subject, the presence of a high number of variables such as human age, metabolism, the presence of alcohol, the complex wine chemistry, and the wide array of in vivo biological effects of these compounds suggest that only cautious conclusions may be drawn from studies focusing on the direct effect of wine and any specific health issue. Nevertheless, there are several reports on the health protective properties of wine phenolics for several diseases such as cardiovascular diseases, some cancers, obesity, neurodegenerative diseases, diabetes, allergies and osteoporosis. The different interactions that wine flavonoids may have with key biological targets are crucial for some of these health-promoting effects. The interaction between some wine flavonoids and some specific enzymes are one example. The way wine flavonoids may be absorbed and metabolized could interfere with their bioavailability and therefore in their health-promoting effect. Hence, some reports have focused on flavonoids absorption, metabolism, microbiota effect and overall on flavonoids bioavailability. This review summarizes some of these major issues which are directly related to the potential health-promoting effects of wine flavonoids. Reports related to flavonoids and health highlight some relevant scientific information. However, there is still a gap between the knowledge of wine flavonoids bioavailability and their health-promoting effects. More in vivo results as well as studies focused on flavonoid metabolites are still required. Moreover, it is also necessary to better understand how biological interactions (with microbiota and cells, enzymes or general biological systems) could interfere with flavonoid bioavailability.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81878703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Architecture of Thiol Antioxidant Systems among Invertebrate Parasites","authors":"A. Guevara-Flores, J. Martínez-González, J. Rendón, I. P. del Arenal","doi":"10.3390/molecules22020259","DOIUrl":"https://doi.org/10.3390/molecules22020259","url":null,"abstract":"The use of oxygen as the final electron acceptor in aerobic organisms results in an improvement in the energy metabolism. However, as a byproduct of the aerobic metabolism, reactive oxygen species are produced, leaving to the potential risk of an oxidative stress. To contend with such harmful compounds, living organisms have evolved antioxidant strategies. In this sense, the thiol-dependent antioxidant defense systems play a central role. In all cases, cysteine constitutes the major building block on which such systems are constructed, being present in redox substrates such as glutathione, thioredoxin, and trypanothione, as well as at the catalytic site of a variety of reductases and peroxidases. In some cases, the related selenocysteine was incorporated at selected proteins. In invertebrate parasites, antioxidant systems have evolved in a diversity of both substrates and enzymes, representing a potential area in the design of anti-parasite strategies. The present review focus on the organization of the thiol-based antioxidant systems in invertebrate parasites. Differences between these taxa and its final mammal host is stressed. An understanding of the antioxidant defense mechanisms in this kind of parasites, as well as their interactions with the specific host is crucial in the design of drugs targeting these organisms.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74133719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats","authors":"Hyun-Jong Cho, Jun-Pil Jee, Ji-Ye Kang, D. Shin, Han‐Gon Choi, H. Maeng, K. Cho","doi":"10.3390/molecules22020280","DOIUrl":"https://doi.org/10.3390/molecules22020280","url":null,"abstract":"The aim of this work was to develop cefdinir solid dispersions (CSDs) prepared using hydrophilic polymers with enhanced dissolution/solubility and in vivo oral bioavailability. CSDs were prepared with hydrophilic polymers such as hydroxypropyl-methylcellulose (HPMC; CSD1), carboxymethylcellulose-Na (CMC-Na; CSD2), polyvinyl pyrrolidone K30 (PVP K30; CSD3) at the weight ratio of 1:1 (drug:polymer) using a spray-drying method. The prepared CSDs were characterized by aqueous solubility, differential scanning calorimetry (DSC), powder X-ray diffraction (p-XRD), scanning electron microscopy (SEM), aqueous viscosity, and dissolution test in various media. The oral bioavailability of CSDs was also evaluated in rats and compared with cefdinir powder suspension. The cefdinir in CSDs was amorphous form, as confirmed in the DSC and p-XRD measurements. The developed CSDs commonly resulted in about 9.0-fold higher solubility of cefdinir and a significantly improved dissolution profile in water and at pH 1.2, compared with cefdinir crystalline powder. Importantly, the in vivo oral absorption (represented as AUCinf) was markedly increased by 4.30-, 6.77- and 3.01-fold for CSD1, CSD2, and CSD3, respectively, compared with cefdinir suspension in rats. The CSD2 prepared with CMC-Na would provide a promising vehicle to enhance dissolution and bioavailability of cefdinir in vivo.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"92 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86646875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure and Conformational Properties of d-Glucose/d-Galactose-Binding Protein in Crowded Milieu","authors":"A. Fonin, S. Silonov, Asiya K. Sitdikova, I. Kuznetsova, V. Uversky, K. Turoverov","doi":"10.3390/molecules22020244","DOIUrl":"https://doi.org/10.3390/molecules22020244","url":null,"abstract":"Conformational changes of d-glucose/d-galactose-binding protein (GGBP) were studied under molecular crowding conditions modeled by concentrated solutions of polyethylene glycols (PEG-12000, PEG-4000, and PEG-600), Ficoll-70, and Dextran-70, addition of which induced noticeable structural changes in the GGBP molecule. All PEGs promoted compaction of GGBP and lead to the increase in ordering of its structure. Concentrated solutions of PEG-12000 and PEG-4000 caused GGBP aggregation. Although Ficoll-70 and Dextran-70 also promoted increase in the GGBP ordering, the structural outputs were different for different crowders. For example, in comparison with the GGBP in buffer, the intrinsic fluorescence spectrum of this protein was shifted to short-wave region in the presence of PEGs but was red-shifted in the presence of Ficoll-70 and Dextran-70. It was hypothesized that this difference could be due to the specific interaction of GGBP with the sugar-based polymers (Ficoll-70 and Dextran-70), indicating that protein can adopt different conformations in solutions containing molecular crowders of different chemical nature. It was also shown that all tested crowding agents were able to stabilize GGBP structure shifting the GGBP guanidine hydrochloride (GdnHCl)-induced unfolding curves to higher denaturant concentrations, but their stabilization capabilities did not depend on the hydrodynamic dimensions of the polymers molecules. Refolding of GGBP was complicated by protein aggregation in all tested solutions of crowding agents. The lowest yield of refolded protein was achieved in the highly concentrated solutions of PEG-12000. These data support the previous notion that the influence of macromolecular crowders on proteins is rather complex phenomenon that extends beyond the excluded volume effects.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89887959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trypanocidal Activity of Quinoxaline 1,4 Di-N-oxide Derivatives as Trypanothione Reductase Inhibitors","authors":"K. F. Chacón-Vargas, B. Nogueda-Torres, L. Sánchez-Torres, Erick Suárez-Contreras, Juan C Villalobos-Rocha, Yuridia Torres-Martínez, E. E. Lara-Ramírez, G. Fiorani, R. Krauth-Siegel, M. Bolognesi, A. Monge, G. Rivera","doi":"10.3390/molecules22020220","DOIUrl":"https://doi.org/10.3390/molecules22020220","url":null,"abstract":"Chagas disease or American trypanosomiasis is a worldwide public health problem. In this work, we evaluated 26 new propyl and isopropyl quinoxaline-7-carboxylate 1,4-di-N-oxide derivatives as potential trypanocidal agents. Additionally, molecular docking and enzymatic assays on trypanothione reductase (TR) were performed to provide a basis for their potential mechanism of action. Seven compounds showed better trypanocidal activity on epimastigotes than the reference drugs, and only four displayed activity on trypomastigotes; T-085 was the lead compound with an IC50 = 59.9 and 73.02 µM on NINOA and INC-5 strain, respectively. An in silico analysis proposed compound T-085 as a potential TR inhibitor with better affinity than the natural substrate. Enzymatic analysis revealed that T-085 inhibits parasite TR non-competitively. Compound T-085 carries a carbonyl, a CF3, and an isopropyl carboxylate group at 2-, 3- and 7-position, respectively. These results suggest the chemical structure of this compound as a good starting point for the design and synthesis of novel trypanocidal derivatives with higher TR inhibitory potency and lower toxicity.","PeriodicalId":19033,"journal":{"name":"Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83571649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}