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排序方式: 共有158条查询结果,搜索用时 15 毫秒
51.
Dr. Rakesh K. Pathak Christopher D. McNitt Prof. Dr. Vladimir V. Popik Prof. Dr. Shanta Dhar 《Chemistry (Weinheim an der Bergstrasse, Germany)》2014,20(23):6861-6865
The ability to rationally design and construct a platform technology to develop new platinum(IV) [PtIV] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well‐defined chemistry is critical for discovering new platinum‐based therapeutics. With limited numbers of possibilities considering the sensitivity of PtIV centers, we used a strain‐promoted azide–alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single PtIV precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated. 相似文献
52.
Prof. Robert M. Hughes Christina M. Marvin Dr. Zachary L. Rodgers Dr. Song Ding Dr. Nathan P. Oien Dr. Weston J. Smith Prof. David S. Lawrence 《Angewandte Chemie (International ed. in English)》2016,55(52):16080-16083
A strategy for the light‐activated release of bioactive compounds (BODIPY, colchicine, paclitaxel, and methotrexate) from membrane‐enclosed depots is described. We have found that membrane‐permeable bioagents can be rendered membrane impermeable by covalent attachment to cobalamin (Cbl) through a photocleavable linker. These Cbl‐bioagent conjugates are imprisoned within lipid‐enclosed compartments in the dark, as exemplified by their retention in the interior of erythrocytes. Subsequent illumination drives the secretion of the bioactive species from red blood cells. Photorelease is triggered by wavelengths in the red, far‐red, and near‐IR regions, which can be pre‐assigned by affixing a fluorophore with the desired excitation wavelength to the Cbl‐bioagent conjugate. Pre‐assigned wavelengths allow different biologically active compounds to be specifically and unambiguously photoreleased from common carriers. 相似文献
53.
Self-immolative dendrimers are a unique class of molecules that are able to disassemble upon undergoing a specific triggering reaction through domino-like fragmentations. We have designed and synthesized a novel AB(6) self-immolative dendritic adaptor that amplifies a single cleavage event into the release of six reporter units. The disassembly mechanism is based on a specifically triggered cleavage event followed by elimination of a cyclic urea derivative and six consecutive quinone methide eliminations. The system was disassembled under both organic and aqueous conditions by either chemical or enzymatic triggering. Various reporter molecules and triggering groups were introduced onto the dendritic adaptor to obtaining sensor molecules with enhanced properties for diagnostics and imaging. 相似文献
54.
Metabolic reactions that occur at alkylamino moieties may provide insight into the roles of these moieties when they are parts of drug molecules that act at different receptors. N-dealkylation of N,N-dialkylamino moieties has been associated with retaining, attenuation or loss of pharmacologic activities of metabolites compared to their parent drugs. Further, N-dealkylation has resulted in clinically used drugs, activation of prodrugs, change of receptor selectivity, and providing potential for developing fully-fledged drugs. While both secondary and tertiary alkylamino moieties (open chain aliphatic or heterocyclic) are metabolized by CYP450 isozymes oxidative N-dealkylation, only tertiary alkylamino moieties are subject to metabolic N-oxidation by Flavin-containing monooxygenase (FMO) to give N-oxide products. In this review, two aspects will be examined after surveying the metabolism of representative alkylamino-moieties-containing drugs that act at various receptors (i) the pharmacologic activities and relevant physicochemical properties (basicity and polarity) of the metabolites with respect to their parent drugs and (ii) the role of alkylamino moieties on the molecular docking of drugs in receptors. Such information is illuminative in structure-based drug design considering that fully-fledged metabolite drugs and metabolite prodrugs have been, respectively, developed from N-desalkyl and N-oxide metabolites. 相似文献
55.
An N‐Acetyl Cysteine Ruthenium Tricarbonyl Conjugate Enables Simultaneous Release of CO and Ablation of Reactive Oxygen Species
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Dr. João D. Seixas Dr. Miguel Chaves‐Ferreira Diana Montes‐Grajales Ana M. Gonçalves Dr. Ana R. Marques Dr. Lígia M. Saraiva Prof. Jesus Olivero‐Verbel Prof. Carlos C. Romão Dr. Gonçalo J. L. Bernardes 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(42):14708-14712
We have designed and synthesised a [Ru(CO)3Cl2(NAC)] pro‐drug that features an N‐acetyl cysteine (NAC) ligand. This NAC carbon monoxide releasing molecule (CORM) conjugate is able to simultaneously release biologically active CO and to ablate the concurrent formation of reactive oxygen species (ROS). Complexes of the general formulae [Ru(CO)3(L)3]2+, including [Ru(CO)3Cl(glycinate)] (CORM‐3), have been shown to produce ROS through a water–gas shift reaction, which contributes significantly, for example, to their antibacterial activity. In contrast, NAC‐CORM conjugates do not produce ROS or possess antibacterial activity. In addition, we demonstrate the synergistic effect of CO and NAC both for the inhibition of nitric oxide (formation) and in the expression of tumour‐necrosis factor (TNF)‐α. This work highlights the advantages of combining a CO‐releasing scaffold with the anti‐oxidant and anti‐inflammatory drug NAC in a unique pro‐drug. 相似文献
56.
Ring‐Opening Polymerization of Prodrugs: A Versatile Approach to Prepare Well‐Defined Drug‐Loaded Nanoparticles
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Dr. Jinyao Liu Dr. Wenge Liu Isaac Weitzhandler Dr. Jayanta Bhattacharyya Dr. Xinghai Li Dr. Jing Wang Yizhi Qi Dr. Somnath Bhattacharjee Dr. Ashutosh Chilkoti 《Angewandte Chemie (International ed. in English)》2015,54(3):1002-1006
The synthesis of polymer–drug conjugates from prodrug monomers consisting of a cyclic polymerizable group that is appended to a drug through a cleavable linker is achieved by organocatalyzed ring‐opening polymerization. The monomers polymerize into well‐defined polymer prodrugs that are designed to self‐assemble into nanoparticles and release the drug in response to a physiologically relevant stimulus. This method is compatible with structurally diverse drugs and allows different drugs to be copolymerized with quantitative conversion of the monomers. The drug loading can be controlled by adjusting the monomer(s)/initiator feed ratio and drug release can be encoded into the polymer by the choice of linker. Initiating these monomers from a poly(ethylene glycol) macroinitiator results in amphiphilic diblock copolymers that spontaneously self‐assemble into micelles with a long plasma circulation, which is useful for systemic therapy. 相似文献
57.
Prof. Jana Kasparkova Dr. Hana Kostrhunova Dr. Olga Novakova Dr. Radka Křikavová Dr. Ján Vančo Prof. Zdeněk Trávníček Prof. Viktor Brabec 《Angewandte Chemie (International ed. in English)》2015,54(48):14478-14482
We report toxic effects of a photoactivatable platinum(IV) complex conjugated with suberoyl‐bis‐hydroxamic acid in tumor cells. The conjugate exerts, after photoactivation, two functions: activity as both a platinum(II) anticancer drug and histone deacetylase (HDAC) inhibitor in cancer cells. This approach relies on the use of a PtIV pro‐drug, acting by two independent mechanisms of biological action in a cooperative manner, which can be selectively photoactivated to a cytotoxic species in and around a tumor, thereby increasing selectivity towards cancer cells. These results suggest that this strategy is a valuable route to design new platinum agents with higher efficacy for photodynamic anticancer chemotherapy. 相似文献
58.
59.
Dr. Shiyu Zhou Prof. Xiuli Hu Dr. Rui Xia Shi Liu Qing Pei Prof. Guang Chen Prof. Zhigang Xie Prof. Xiabin Jing 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(51):23398-23405
The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia-activated self-immolative prodrug of paclitaxel (PTX2-Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light-boosted PTX nanoparticle (Ce6/PTX2-Azo NP). In this nanoparticle, PTX2-Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy. 相似文献
60.
N Barraud BG Kardak NR Yepuri RP Howlin JS Webb SN Faust S Kjelleberg SA Rice MJ Kelso 《Angewandte Chemie (International ed. in English)》2012,51(36):9057-9060
Just say NO to biofilms: NO-donors are used to disperse a bacterial biofilm so that co-administered antibiotics will kill the more susceptible unattached cells. The chemically stable cephalosporin-3'-diazeniumdiolate NO-donor prodrug is activated by bacterial β-lactamases and facilitates this two-step biofilm erradication. 相似文献