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33.
王普善 《精细与专用化学品》2001,9(10):12-15
世界天然药物市场主要集中在美国、欧洲和亚洲三大区域,全球植物药市场的年销售额已达270亿美元。在过去的10年间,以植物制剂为主体的天然药物开始走俏西方。面对“回归自然”的世界潮流,采用现代科学技术,实现中药现代化和国际化,将为人类现代医疗保健做出重大贡献。 相似文献
34.
Prof. Michael Murray Dr. Ariane Roseblade Dr. Yongjuan Chen Kirsi Bourget Dr. Tristan Rawling 《ChemMedChem》2020,15(2):247-255
Targeting the tumor cell mitochondrion could produce novel anticancer agents. We designed an aryl−urea fatty acid ( 1 g ; 16({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)hexadecanoic acid) that disrupted the mitochondrion and decreased MDA-MB-231 breast cancer cell viability. To optimize the aryl−ureas the present study evaluated mitochondrial targeting by 1 g analogues containing alkyl chains between 10–17 carbons. Using the dye JC-1, the C12−C17 analogues efficiently disrupted the mitochondrial membrane potential (IC50s 3.5±1.2 to 7.6±1.1 μM) and impaired ATP production; shorter analogues were less active. 7-Aminoactinomycin D/annexin V staining and flow cytometry showed that these agents activated the killing mechanisms of necrosis and apoptosis to varying extents (7-aminoactinomycin D/annexin V staining ratios 4.3–6.0). Indeed, 1 g and its C17 analogue preferentially activated necrosis and apoptosis, respectively (ratios 2.1 and 16). Taken together, alkyl chain length is a determinant of mitochondrial targeting by aryl−ureas and can be varied to develop analogues that activate apoptosis or necrosis in a regulated fashion. 相似文献
35.
Purushottam B. Tiwari Prem P. Chapagain Ahmed Seddek Thirunavukkarasu Annamalai Aykut Üren Yuk-Ching Tse-Dinh 《ChemMedChem》2020,15(7):623-631
A topoisomerase-DNA transient covalent complex can be a druggable target for novel topoisomerase poison inhibitors that represent a new class of antibacterial or anticancer drugs. Herein, we have investigated molecular features of the functionally important Escherichia coli topoisomerase I (EctopoI)-DNA covalent complex (EctopoIcc) for molecular simulations, which is very useful in the development of new antibacterial drugs. To demonstrate the usefulness of our approach, we used a model small molecule (SM), NSC76027, obtained from virtual screening. We examined the direct binding of NSC76027 to EctopoI as well as inhibition of EctopoI relaxation activity of this SM via experimental techniques. We then performed molecular dynamics (MD) simulations to investigate the dynamics and stability of EctopoIcc and EctopoI-NSC76027-DNA ternary complex. Our simulation results show that NSC76027 forms a stable ternary complex with EctopoIcc. EctopoI investigated here also serves as a model system for investigating a complex of topoisomerase and DNA in which DNA is covalently attached to the protein. 相似文献
36.
Poly(ε-caprolactone) (PCL) is a bioresorbable and biocompatible polymer with assorted medical applications. However, remarkable hydrophobicity and nonosteoconductivity have stood as a barrier to limit its applications. The present study aims to modify the bulk characteristics of PCL to develop a polymeric scaffold with adequate structural and mechanical properties to support regenerated tissues. For this purpose, functionalized bacterial cellulose nanowhiskers (BCNW-g-βCD-PCL2000) are synthesized. Reinforcing PCL matrix with 4 wt % of the nanowhiskers resulted in a bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite shows improvements of 115 and 51% in tensile strength and Young's modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous structures of 86–95% porosity with interconnected macropores of mean pore diameters of 250–420 μm. Porous scaffolds showed compression modulus values of 5.3–9.1 MPa and would have promising applications in regenerative medicine. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48481. 相似文献
37.
Exploring the Effects of Glycosylation and Etherification of the Side Chains of the Anticancer Drug Mitoxantrone 下载免费PDF全文
Pazit Shaul Kfir B. Steinbuch Eran Blacher Prof. Reuven Stein Dr. Micha Fridman 《ChemMedChem》2015,10(9):1528-1538
Herein we report the synthesis and biological evaluation of symmetric and asymmetric analogues of the DNA intercalating drug mitoxantrone (MTX) in which the side chains of the parent drug were modified through glycosylation or methyl etherification. Several analogues with glycosylated side chains exhibited higher DNA affinity than the parent MTX. The most potent in vitro cytotoxicity was observed for MTX analogue 8 (1,4‐dimethoxy‐5,8‐bis[2‐(2‐methoxyethylamino)ethylamino]anthracene‐9,10‐dione) with methoxy ether containing side chains. Treatment of melanoma‐bearing mice with MTX or analogue 8 decreased the intraperitoneal tumor burden relative to untreated mice; the effect of 8 was less pronounced than that of MTX. In vitro metabolism assays of MTX with rabbit liver S9 fraction gave rise to several metabolites; almost no metabolites were detected for MTX analogue 8 . The results presented indicate that derivatization of the MTX side chain primary hydroxy groups may result in a significant improvement in DNA affinity and lower susceptibility to the formation of potentially toxic metabolites. 相似文献
38.
Dr. Marie Monestier Peggy Charbonnier Dr. Christelle Gateau Dr. Martine Cuillel Faustine Robert Colette Lebrun Dr. Elisabeth Mintz Prof. Olivier Renaudet Dr. Pascale Delangle 《Chembiochem : a European journal of chemical biology》2016,17(7):590-594
Liver cells are an essential target for drug delivery in many diseases. The hepatocytes express the asialoglycoprotein receptor (ASGPR), which promotes specific uptake by means of N‐acetylgalactosamine (GalNAc) recognition. In this work, we designed two different chemical architectures to treat Wilson's disease by intracellular copper chelation. Two glycoconjugates functionalized with three or four GalNAc units each were shown to enter hepatic cells and chelate copper. Here, we studied two series of compounds derived from these glycoconjugates to find key parameters for the targeting of human hepatocytes. Efficient cellular uptake was demonstrated by flow cytometry using HepG2 human heptic cells that express the human oligomeric ASGPR. Dissociation constants in the nanomolar range showed efficient multivalent interactions with the receptor. Both architectures were therefore concluded to be able to compete with endogeneous asialoglycoproteins and serve as good vehicles for drug delivery in hepatocytes. 相似文献
39.
Ambrish Kumar Srivastava Anoop Kumar Pandey Saurabh Pandey 《Polycyclic Aromatic Compounds》2016,36(4):452-466
In this article, we made a comparative study of two multiple myeloma drugs: lenalidomide and pomalidomide. We calculated and discussed their geometries at DFT/B3LYP method. Intra-molecular hydrogen bonding in these molecules is confirmed and characterized by QTAIM calculations. Electronic parameters along with HOMO-LUMO and MESP surfaces are calculated in order to compare their chemical reactivity. The effect of structure and bonding on electronic properties and biological activities is discussed and it is established that pomalidomide is more biologically active than lenalidomide. The phenyl ring of these molecules show teratogenic effects, making a possibility of finding another new class of drugs. 相似文献
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