Search results for "combinatorial"
showing 10 items of 1208 documents
Potential and challenges in home care service process optimization : a route optimization approach
2016
Aging of the population is an increasing problem in many countries, including Finland, and it poses a challenge to public services such as home care. Vehicle routing optimization (VRP) type optimization solutions are one possible way to decrease the time required for planning home visits and driving to customer addresses, as well as decreasing transportation costs. Although VRP optimization is widely and succesfully applied to commercial and industrial logistics, the home care is a relatively new application area for it. This thesis examines what kind of distance and time savings would be possible to achieve if daily home care operations are optimized in the similar manner as typical VRP op…
Structural characterization of site-modified nanocapsid with monodispersed gold clusters
2017
AbstractHepatitis E Virus-like particles self-assemble in to noninfectious nanocapsids that are resistant to proteolytic/acidic mucosal delivery conditions. Previously, the nanocapsid was engineered to specifically bind and enter breast cancer cells, where successful tumor targeting was demonstrated in animal models. In the present study, the nanocapsid surface was modified with a solvent-exposed cysteine to conjugate monolayer protected gold nanoclusters (AuNC). Unlike commercially available gold nanoparticles, AuNCs monodisperse in water and are composed of a discrete number of gold atoms, forming a crystalline gold core. Au102pMBA44 (Au102) was an ideal conjugate given its small 2.5 nm s…
Synthesis of alkyl-5,8-dimethyl-6-phenyl-5,6-dihydropyrazolo[3,4-f] [1,2,3,5]tetrazepin-4(3H)-ones of pharmaceutical interest
2006
The multistep synthesis of two pyrazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one derivatives, a new class of fused 1,2,3,5-tetrazepinones with potential antiproliferative activity, has been carried out. Owing to the instability of the above compounds, the last step of the synthesis was performed at -5/0 degrees C. The obtained tetrazepinones, when allowed to stand at r.t. for 24 h, afforded quantitatively 1-phenyl-3,6-dimethylpyrazolo [3,4-d][1,2,3] triazole.
Glycosidopyrroles. Part 4. 1-β-D-ribofuranosyl-pyrroles and indoles as potential antiviral agents
2000
The preparation of new 1-β-D-ribofuranosylpyrroles of type 8 and a new method of synthesis of 1-β-D-ribofuranosylindoles of type 10, according to the scheme, is reported. All these new derivatives showed promising chemical and physical analogies with bioactive molecules but did not show any antiviral activity againstHIV1.
“One Ring to Bind Them All”—Part II: Identification of Promising G-Quadruplex Ligands by Screening of Cyclophane-Type Macrocycles
2010
A collection of 26 polyammonium cyclophane-type macrocycles with a large structural diversity has been screened for G-quadruplex recognition. A two-step selection procedure based on the FRET-melting assay was carried out enabling identification of macrocycles of high affinity (ΔT1/2up to30°C) and high selectivity for the human telomeric G-quadruplex. The four selected hits possess sophisticated architectures, more particularly the presence of a pendant side-arm as well as the existence of a particular topological arrangement appear to be strong determinants of quadruplex binding. These compounds are thus likely to create multiple contacts with the target that may be at the origin of their h…
Hapten Design and Antibody Generation for Immunoanalysis of Spirotetramat and Spirotetramat-enol
2018
Spirotetramat - a tetramic acid insecticide - is rapidly metabolized or degraded to give spirotetramat-enol; so, common residue definitions include the sum of both compounds. In the present study, two spirotetramat-functionalized derivatives (haptens) have been designed to generate immunoreagents to these molecules for rapid immunochemical analysis. Haptens have been synthesized with alternative linker tethering sites and, for the first time, high-affinity antibodies have been generated with different specificities to these active principles. Two sensitive assays have been developed using the same antibody in different formats, and by using linker-site heterologous haptens, the selectivity …
Synthesis, computational evaluation and pharmacological assessment of acetylsalicylic esters as anti-inflammatory agents
2019
A convenient approach to the synthesis of alkyl esters of aspirin (ASA-OR) has been developed. The synthesis of ASA-OR has been realized in two steps: (1) direct esterification of salicylic acid with alcohols in the presence of dicyclohexylcarbodiimide to give alkyl salicylates (SAL-OR); (2) acetylation of SAL-OR with acetyl chloride to yield ASA-OR. Molecular mechanics simulations, performed to calculate the kinetic radii of several ASA-OR, indicated that the pentyl and hexyl acetylsalicylates possess the best properties to cross cell membranes. The in vitro biological tests demonstrate their anti-inflammatory activity, superimposable to that of aspirin. The results of our study suggest th…
Modular Solid-Phase Synthesis of Antiprotozoal Barnesin Derivatives
2020
Here, we applied and optimized a solid support (SP)-based Horner-Wadsworth-Emmons reagent to prepare SP-bound vinylogous amino acids. Subsequent SP-based peptide synthesis, global deprotection, and chemical modifications yielded 14 lipodipeptides carrying vinylogous amino acids, including the natural product barnesin A (1). Biological evaluation revealed that several synthesized derivatives show micromolar to nanomolar inhibitory activity against papain-like cysteine proteases, human cathepsin L, and rhodesain.
Squaric Acid-Based Radiopharmaceuticals for Tumor Imaging and Therapy.
2021
Targeting vectors bound to a chelator represent a significant fraction of radiopharmaceuticals used nowadays for diagnostic and therapeutic purposes in nuclear medicine. The use of squaramides as coupling units for chelator and targeting vector helps to circumvent the disadvantages of several common coupling methods. This review gives an overview of the use of squaric acid diesters (SADE) as linking agents. It focuses on the conjugation of cyclic chelators, e.g., DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), as well as hybrid chelators like AAZTA5 (6-pentanoic acid-6-amino-1,4-diazepine tetracetic acid) or DATA5m (6-pentanoic acid-6-amino-1,4-diazapine-triacetate) to diff…
Recent development in fluorinated antibiotics
2019
This chapter presents the most recent results in the development of fluorinated antibioticsby taking into consideration modern challenges of multidrug-resistant pathogens. After a brief introduction on the direct and indirect effects of fluorine and fluorinated moieties in regulating biological activity, the chapter is developed in three main subsections discussing the two major classes of fluorinated antibiotics, fluoroquinolones and oxazolidinones, plus an overview of recent research on the antibiotic activity of fluorinated analogs of tetracyclines, peptidomimetics, triazoles, and nucleosides. Discussed aspects include: (1) Synthesis and challenges posed by the introduction of fluorinate…