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https://www.readbyqxmd.com/read/29353085/reactions-of-a-tetranuclear-pt-thiosemicarbazone-complex-with-model-proteins
#1
Tiziano Marzo, Francisco Navas, Damiano Cirri, Antonello Merlino, Giarita Ferraro, Luigi Messori, Adoracion G Quiroga
The tetranuclear Pt complex (PtL)4 (where L2- is the anion derived from para-isopropyl thiosemicarbazone) was first described in A.G. Quiroga et al., J. Med. Chem. 41, 1998, 1399-1408. (PtL)4 manifests antiproliferative properties toward various cancer cell lines being a promising anticancer drug candidate. Yet, details of its reactivity with biomolecules have not been elucidated. To this end, we investigated the reactions of (PtL)4 with a few model proteins, i.e. bovine pancreatic ribonuclease (RNase A), cytochrome c (Cyt c) and hen egg white lysozyme (Lysozyme), through electrospray ionization mass spectrometry and other biophysical methods...
January 10, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29352868/alginate-based-cancer-associated-stimuli-driven-and-turn-on-theranostic-prodrug-nanogel-for-cancer-detection-and-treatment
#2
Mingliang Pei, Xu Jia, Xubo Zhao, Jiagen Li, Peng Liu
Alginate-based cancer-associated, stimuli-driven and turn-on theranostic prodrug nanogels were designed for the tumor diagnosis and chemotherapy, by crosslinking the folate-terminated poly(ethylene glycol) (FA-PEG-NH2) and rhodamine B (RhB)-terminated poly(ethylene glycol) (RhB-PEG-NH2) modified oxidized alginate (OAL-g-PEG-FA/RhB) with cystamine (Cys), followed covalent conjugation of doxorubicin (DOX) via acid-labile Schiff base bond. Owing to the surface folic acid (FA) groups, disulfide crosslinking structure and Schiff base conjugation for DOX, the folate receptor (FR)-mediated targeting and pH/reduction dual responsive intracellular triggered release of DOX was achieved...
March 1, 2018: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29352704/treatment-of-adult-chronic-indeterminate-chagas-disease-with-benznidazole-and-three-e1224-dosing-regimens-a-proof-of-concept-randomised-placebo-controlled-trial
#3
Faustino Torrico, Joaquim Gascon, Lourdes Ortiz, Cristina Alonso-Vega, María-Jesús Pinazo, Alejandro Schijman, Igor C Almeida, Fabiana Alves, Nathalie Strub-Wourgaft, Isabela Ribeiro
BACKGROUND: Chagas disease is a major neglected vector-borne disease. In this study, we investigated the safety and efficacy of three oral E1224 (a water-soluble ravuconazole prodrug) regimens and benznidazole versus placebo in adult chronic indeterminate Chagas disease. METHOD: In this proof-of-concept, double-blind, randomised phase 2 clinical trial, we recruited adults (18-50 years) with confirmed diagnosis of Trypanosoma cruzi infection from two outpatient units in Bolivia...
January 15, 2018: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/29350913/environmentally-triggerable-retinoic-acid-inducible-gene-i-agonists-using-synthetic-polymer-overhangs
#4
Christian R Palmer, Max E Jacobson, Olga Fedorova, Anna M Pyle, John T Wilson
Retinoic acid-inducible gene I (RIG-I) is a cytosolic pattern recognition receptor (PRR) that potently activates antiviral innate immunity upon recognition of 5' triphosphorylated double-stranded RNA (pppRNA). Accordingly, RNA ligands of the RIG-I pathway have recently emerged as promising antiviral agents, vaccine adjuvants, and cancer immunotherapeutics. However, RIG-I is expressed constitutively in virtually all cell types, and therefore administration of RIG-I agonists causes risk for systemic inflammation and possible dose-limiting toxicities...
January 19, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29350904/nanoplatform-assembled-from-a-cd44-targeted-prodrug-and-smart-liposomes-for-dual-targeting-of-tumor-microenvironment-and-cancer-cells
#5
Yaqi Lv, Chaoran Xu, Xiangmei Zhao, Chenshi Lin, Xin Yang, Xiaofei Xin, Li Zhang, Chao Qin, Xiaopeng Han, Lei Yang, Wei He, Lifang Yin
The tumor microenvironment (TME) plays a critical role in tumor initiation, progression, invasion and metastasis. Therefore, a therapy that combines chemotherapeutic drugs with a TME modulator could be a promising route for cancer treatment. This paper reports a nanoplatform self-assembled from a hyaluronic acid (HA)-paclitaxel (PTX) (HA-PTX) prodrug and marimastat (MATT)-loaded thermosensitive liposomes (LTSLs) (MATT-LTSLs) for the dual targeting of the TME and cancer cells. Interestingly, the prodrug HA-PTX can self-assemble on both positively and negatively charged liposomes, forming hybrid nanoparticles (HNPs, 100 nm)...
January 19, 2018: ACS Nano
https://www.readbyqxmd.com/read/29350522/chemical-design-of-both-a-glutathione-sensitive-dimeric-drug-guest-and-a-glucose-derived-nanocarrier-host-to-achieve-enhanced-osteosarcoma-lung-metastatic-anticancer-selectivity
#6
Lu Su, Richen Li, Sarosh Khan, Ryan Clanton, Fuwu Zhang, Yen-Nan Lin, Yue Song, Hai Wang, Jingwei Fan, Soleil Hernandez, Andrew S Butters, Gamal Akabani, Ronan MacLoughlin, Justin Smolen, Karen L Wooley
Although nanomedicines have been pursued for nearly 20 years, fundamental chemical strategies that seek to optimize both the drug and drug carrier together in a concerted effort remain uncommon yet may be powerful. In this work, two block polymers and one dimeric prodrug molecule were designed to be coassembled into degradable, functional nanocarriers, where the chemistry of each component was defined to accomplish important tasks. The result is a poly(ethylene glycol) (PEG)-protected redox-responsive dimeric paclitaxel (diPTX)-loaded cationic poly(d-glucose carbonate) micelle (diPTX@CPGC)...
January 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29348806/therapeutic-nanosystem-consisting-of-singlet-oxygen-responsive-prodrug-and-photosensitizer-excited-by-two-photon-light
#7
Yi Lin, Xiao-Fang Jiang, Xiangyan Duan, Fang Zeng, Bo Wu, Shuizhu Wu
Using light as the sole stimulus and employing the generated singlet oxygen as a therapeutic agent and the trigger to activate chemo-drug release could serve as an elegant way to bring into full play the advantageous features of light and enhance therapeutic efficacy through a combination of chemotherapy and photodynamic therapy. Herein a liposomal drug system has been developed by embedding a fluorescent photosensitizer and a prodrug into phospholipid vesicles. Upon one- or two-photon light irradiation, the photosensitizer generates singlet oxygen, which removes the protecting group of the prodrug and subsequently causes the release of the active drug chlorambucil...
January 11, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29348616/fast-and-effective-mitochondrial-delivery-of-%C3%AF-rhodamine-b-polysulfobetaine-peg-copolymers
#8
Nobuyuki Morimoto, Riho Takei, Masaru Wakamura, Yoshifumi Oishi, Masafumi Nakayama, Makoto Suzuki, Masaya Yamamoto, Françoise M Winnik
Mitochondrial targeting and entry, two crucial steps in fighting severe diseases resulting from mitochondria dysfunction, pose important challenges in current nanomedicine. Cell-penetrating peptides or targeting groups, such as Rhodamine-B (Rho), are known to localize in mitochondria, but little is known on how to enhance their effectiveness through structural properties of polymeric carriers. To address this issue, we prepared 8 copolymers of 3-dimethyl(methacryloyloxyethyl)ammonium propane sulfonate and poly(ethyleneglycol) methacrylate, p(DMAPS-ran-PEGMA) (molecular weight, 18...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346736/light-activatable-red-blood-cell-membrane-camouflaged-dimeric-prodrug-nanoparticles-for-synergistic-photodynamic-chemotherapy
#9
Qing Pei, Xiuli Hu, Xiaohua Zheng, Shi Liu, Yawei Li, Xiabin Jing, Zhigang Xie
Biomimetic approach offers numerous opportunities to design therapeutic platforms with enhanced antitumor performance and biocompatibility. Herein we report a novel red blood cell membrane-camouflaged nanoparticle (RBC(M(TPC-PTX))) for synergistic chemo- and photodynamic therapy (PDT). Specifically, the inner core is mainly constructed by reactive oxygen species (ROS)-responsive PTX dimer (PTX2-TK) and photosensitizer 5,10,15,20-tetraphenylchlorin (TPC). In vitro experiments show that the prepared RBC(M(TPC-PTX)) is readily taken up into endosomes...
January 18, 2018: ACS Nano
https://www.readbyqxmd.com/read/29346131/toxicological-profile-and-safety-pharmacology-of-a-single-dose-of-fibroblast-activation-protein-%C3%AE-based-doxorubicin-prodrug-in-vitro-and-in-vivo-evaluation
#10
Sichao Huang, Yuchen Zhang, Jinsong Zhong, Ying Pan, Shaohui Cai, Jun Xu
Fibroblast activation protein-α (FAPα) is a promising tumor-associated target expressed by reactive stromal fibroblasts in tumor tissue. FAPα has a postprolyl peptidase activity and can specifically cleave N-terminal benzyloxycarbonyl (Z)-blocked peptides, such as the substrate Z-Gly-Pro-AMC. Doxorubicin (DOX) is an effective antitumor drug, but its application is greatly limited by toxic adverse effects owing to poor tumor selectivity. Based on these facts, we previously designed a FAPα-targeting prodrug of doxorubicin (FTPD) which can be selectively hydrolyzed by FAPα...
January 17, 2018: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29342859/multinuclear-nmr-measurements-and-dft-calculations-for-capecitabine-tautomeric-form-assignment-in-a-solution
#11
Piotr Cmoch, Piotr Krzeczyński, Andrzej Leś
The molecular structure of capecitabine (a widely applied prodrug of 5-fluorouracil) was studied by multinuclear NMR measurements and DFT quantum mechanical calculations. One or two tautomeric forms in a solution were detected depending on the solvent used. In the organic solvents, a mixture of two forms of capecitabine was observed: carbamate and imine tautomers. In the aqueous solution, only the carbamate form was found. The methylation of capecitabine yields mainly two products in different proportions: N³-methylcapecitabine and N⁷-methylcapecitabine...
January 13, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29340219/a-novel-hybrid-promoter-are-htert-for-cancer-gene-therapy
#12
S V Kalinichenko, M V Shepelev, P N Vikhreva, I V Korobko
describe a novel hybrid tumor-specific promoter, ARE-hTERT, composed of the human TERT gene promoter (hTERT) and the antioxidant response element (ARE) from the human GCLM gene promoter. The hybrid promoter retains the tumor specificity of the basal hTERT promoter but is characterized by an enhanced transcriptional activity in cancer cells with abnormal activation of the Nrf2 transcription factor and upon induction of oxidative stress. In the in vitro enzyme-prodrug cancer gene therapy scheme, ARE-hTERT promoter-driven expression of CD : UPRT (yeast cytosine deaminase : uracil phosphoribosyltransferase) chimeric protein induced a more pronounced death of cancer cells either upon treatment with 5-fluorouracil (5FC) alone or when 5FC was combined with chemotherapeutic drugs as compared to the hTERT promoter...
October 2017: Acta Naturae
https://www.readbyqxmd.com/read/29339228/stability-and-plasmatic-protein-binding-of-novel-zidovudine-prodrugs-targeting-site-ii-of-human-serum-albumin
#13
Esteban M Schenfeld, Sergio R Ribone, Mario A Quevedo
Despite its vastly demonstrated clinical efficacy, zidovudine (AZT) exhibits several suboptimal pharmacokinetic properties. In particular, its short plasmatic half-life (t1/2 ~ 1 h) is related to its low bound fraction to whole plasmatic proteins and in particular to human serum albumin (HSA). The design of prodrugs constitutes a promising strategy to enhance AZT pharmacokinetic properties, including its affinity for HSA. Recently, we reported the synthesis and chemical stability evaluation of three novel prodrugs of AZT obtained by derivatization with dicarboxylic acids (1-3)...
January 12, 2018: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29338933/physiological-based-pharmacokinetic-modeling-to-estimate-in%C3%A2-vivo-ki-of-ketoconazole-on-renal-p-gp-using-human-drug-drug-interaction-study-result-of-fesoterodine-and-ketoconazole
#14
Masayo Oishi, Yuma Takano, Yutaka Torita, Bimal Malhotra, Koji Chiba
This study was conducted to estimate in vivo inhibition constant (Ki) of ketoconazole on renal P-glycoprotein (P-gp) using human drug-drug interaction (DDI) study result of fesoterodine and ketoconazole. Fesoterodine is a prodrug which is extensively hydrolyzed by non-specific esterases to the active metabolite 5-hydroxymethyl tolterodine (5-HMT). 5-HMT is then further metabolized via Cytochrome P450 (CYP) 2D6 and CYP3A4. It is reported that 5-HMT is a substrate of P-gp whereas fesoterodine is not. Renal clearance of 5-HMT is approximately two-times greater than renal glomerular filtration rate...
November 15, 2017: Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29338573/triphenylphosphine-docetaxel-conjugate-incorporated-albumin-nanoparticles-for-cancer-treatment
#15
Gantumur Battogtokh, Oyuntuya Gotov, Jee He Kang, Jinsung Cho, Tae Ho Jeong, Ganzorig Chimed, Young Tag Ko
AIM: The objective of this study was to develop a mitochondria-targeted anticancer drug, docetaxel (DTX), for chemotherapy. MATERIALS & METHODS: The DTX was conjugated to 4-carboxybutyl triphenylphosphonium (TPP) to enhance mitochondrial targeting, and the TPP-DTX conjugate was further loaded into folate-cholesteryl albumin (FA-chol-BSA) nanoparticles (NPs) to improve its biocompatibility. RESULTS & CONCLUSION: In vitro studies showed that TPP-DTX and its NP primarily accumulated in the mitochondria; generated high reactive oxygen species, leading to mitochondrial disruption and cell apoptosis; and had a higher cytotoxicity against cancer cells...
January 17, 2018: Nanomedicine
https://www.readbyqxmd.com/read/29338458/tenofovir-alafenamide-taf-treatment-of-hbv-what-are-the-unanswered-questions
#16
Mauro Viganò, Alessandro Loglio, Glenda Grossi, Pietro Lampertico
Tenofovir disoproxil fumarate (TDF), an ester prodrug of tenofovir (TFV), is one of the recommended drugs for chronic hepatitis B (CHB) patients. However, reduced kidney function and loss of bone mineral density have been reported in some CHB patients treated with TDF. Consequent to these safety issues, tenofovir alafenamide (TAF) [Vemlidy®], a phosphonate prodrug of TFV, was developed for the treatment of CHB patients. Areas covered: The favourable pharmacological profile of TAF allows a marked reduction in dosage (25 mg/day) thus reducing systemic exposure to tenofovir and improving the bone and renal safety, keeping however the same virological efficacy, compared to TDF 300 mg/day...
January 17, 2018: Expert Review of Anti-infective Therapy
https://www.readbyqxmd.com/read/29337165/establishment-of-intracellular-tenofovir-diphosphate-as-the-key-determinant-for-in-vitro-in-vivo-translation-of-antiviral-efficacy
#17
Bennett Ma, Aline Barth, Carolyn M McHale, Ming-Tain Lai
In vitro evaluation of tenofovir disproxil fumarate (TDF) and tenofovir alafenamide (TAF) revealed comparable antiviral effects with respect to the tenofovir-diphosphate (TFV-DP) level in human peripheral blood mononuclear cells (PBMCs), despite the EC50 values determined based on prodrug concentrations were nearly two orders of magnitude apart. In vivo EC50 obtained from meta-analyses were in good agreement with the in vitro results, indicating intracellular TFV-DP can be employed for in vitro-in vivo translation of viral inhibition for tenofovir prodrugs...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29337163/utility-of-ultra-deep-sequencing-for-detection-of-varicella-zoster-virus-antiviral-resistance-mutations
#18
Mélanie Mercier-Darty, David Boutolleau, Raphaël Lepeule, Christophe Rodriguez, Sonia Burrel
We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyclovir-resistant VZV infection initially detected by Sanger sequencing within a deeply immunocompromised heart transplant recipient. As added-value compared to Sanger analysis, UDS revealed complex dynamics of viral population under antiviral pressure. Varicella-zoster virus (VZV) is a ubiquitous human herpesvirus affecting populations worldwide. VZV is commonly acquired in youth whose primary infection usually manifests as benign varicella (chickenpox)...
January 11, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29336673/a-practical-synthesis-of-xylo-and-arabinofuranoside-precursors-by-diastereoselective-reduction-using-corey-bakshi-shibata-catalyst
#19
Lynn M Utley, Jessica Maldonado, Ahmed M Awad
The Corey-Bakshi-Shibata (CBS) catalyst provides an efficient mechanism to reduce ketones and achieve desired enantiopure alcohols. Herein, the diastereoselective reduction of C-2' and C-3'-keto ribofuranoside derivatives to the corresponding arabino- and xylofuranosides in greater than 95% diastereomeric excess is reported. The stereo-directed substitution with an azido group as well as the synthesis of prodrugs cytarabine and vidarabine are also described. The reported strategy offers superior diastereoselectivity, shorter reaction times, and obviates cooling required with comparable protocols involving achiral reductants...
January 16, 2018: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/29336140/synthesis-of-cisplatin-iv-prodrug-tethered-cufes2-nanoparticles-in-tumor-targeted-chemotherapy-and-photothermal-therapy
#20
Wubshet Mekonnen Girma, Shin-Hwa Tzing, Po-Jen Tseng, Chih-Ching Huang, Yong-Chien Ling, Jia-Yaw Chang
In this study, for the first time, CuFeS2 nanocrystals were successfully prepared through a facile noninjection-based synthetic strategy, by reacting Cu and Fe precursors with dodecanethiol in a 1-octadecene solvent. This one-pot noninjection strategy features easy handling, large-scale production, and high synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2 nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and showed improved biocompatibility, but also possessed a tumor-specific targeting ability of cancer cells bearing the cluster determinant 44 (CD44) receptors...
January 16, 2018: ACS Applied Materials & Interfaces
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