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1.
Vanessa F. M. Carvalho Daniela V. Giacone Leticia V. Costa‐Lotufo Edilberto Rocha Silveira Luciana B. Lopes 《Biomedical chromatography : BMC》2019,33(2)
This study reports the development of a simple and reproducible method, with high rates of recovery, to extract the cytotoxic agent piplartine from skin layers, and a sensitive and rapid UV‐HPLC method for its quantification. Considering the potential of piplartine for topical treatment of skin cancer, this method may find application for formulation development and pharmacokinetics studies to assess cutaneous bioavailability. Porcine skin was employed as a model for human tissue. Piplartine was extracted from the stratum corneum (SC) and remaining viable skin layers (VS) using methanol, vortex homogenization and bath sonication, and subsequently assayed by HPLC using a C18 column, and 1:1 (v/v) acetonitrile–water (adjusted to pH 4.0 with acetic acid 0.1%) as mobile phase. The quantification limit of piplartine was 0.2 μg/mL (0.6 μm ), and the assay was linear up to 5 μg/mL (15.8 μm ), with within‐day and between‐days assay coefficients of variation and relative errors <15%. Piplartine recovery from SC and VS varied from 86 to 96%. The method was suitable to assay samples from skin penetration studies, enabling detection of differences in cutaneous delivery in different skin compartments resulting from treatment with various formulations and time periods. 相似文献
2.
Gabriel Hancu Daniela Lupu Andreea Milan Monica Budu Enik Barabs‐Hajdu 《Biomedical chromatography : BMC》2021,35(1)
Venlafaxine (VFX) is a serotonin and norepinephrine reuptake inhibitor chiral drug used in therapy as an antidepressant in the form of a racemate consisting of R‐ and S‐VFX. The two enantiomers of VFX exhibit different pharmacological activities: R‐VFX inhibits both norepinephrine and serotonin synaptic reuptake, whereas S‐VFX inhibits only the serotonin one. R‐ and S‐VFX are metabolized in the liver to the respective R‐ and S‐O‐desmethylvenlafaxine (ODVFX), R‐ and S‐N‐desmethylvenlafaxine (NDVFX), and R‐ and S‐N,O‐didesmethylvenlafaxine (NODVFX). The pharmacological profile of ODVFX is close to that of VFX, whereas the other two chiral metabolites (NDVFX and NODVFX) have lower affinity for the receptor sites. The pharmacokinetics of the VFX enantiomers appear stereoselective, including the metabolism process. In the past 20 years, several studies describing the enantioselective analysis of R‐ and S‐VFX in pharmaceutical formulations and its chiral metabolites in biological matrices were published. These methods encompass liquid chromatography coupled with UV detection, mass spectrometry, or tandem mass spectrometry, and capillary electrophoresis. This paper reviews the published methods used for the determination of the individual enantiomers of VFX and its chiral metabolites in different matrices. 相似文献
3.
Dr. Giuseppe Ferrauto Dr. Daniela Delli Castelli Dr. Loredana Leone Prof. Mauro Botta Prof. Silvio Aime Dr. Zsolt Baranyai Prof. Lorenzo Tei 《Chemistry (Weinheim an der Bergstrasse, Germany)》2019,25(16):4184-4193
The new ligand HPDO3MA [(R,R,R,R)-10-(2-hydroxypropyl)-α,α′,α′′-trimethyl-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid] was designed to combine and optimize the chemical properties of the macrocyclic ligands HPDO3A and DOTMA. The presence of the methyl groups on the acetic pendant arms of HPDO3A is expected to rigidify the structure of the ligand and favor an increase of the kinetic inertness of the Ln complexes. 1H NMR spectra of Eu(HPDO3MA) displayed the presence of two pairs of diastereoisomers: SAP (square antiprismatic) and TSAP (twisted square antiprismatic) isomers (56 and 44 %, respectively). In addition, 1H and 17O relaxometric NMR studies of Gd(HPDO3MA) showed approximately a 10 % increase in relaxivity and a faster water exchange rate with respect to Gd(HPDO3A). Moreover, a detailed chemical exchange saturation transfer (CEST) characterization of Yb(HPDO3MA) displayed a sensitivity about two times larger than that of Yb(HPDO3A) both in phantom and in cell labeling experiments. Finally, the kinetic inertness of Yb(HPDO3MA) was measured to be twice as high as that of Yb(HPDO3A), with a dissociation half-life at physiological pH of about 2500 years. 相似文献
4.
5.
Synthesis and Biological Evaluation of RGD Peptidomimetic–Paclitaxel Conjugates Bearing Lysosomally Cleavable Linkers 下载免费PDF全文
Alberto Dal Corso Dr. Michele Caruso Dr. Laura Belvisi Dr. Daniela Arosio Prof. Dr. Umberto Piarulli Dr. Clara Albanese Dr. Fabio Gasparri Dr. Aurelio Marsiglio Dr. Francesco Sola Dr. Sonia Troiani Dr. Barbara Valsasina Dr. Luca Pignataro Dr. Daniele Donati Prof. Dr. Cesare Gennari 《Chemistry (Weinheim an der Bergstrasse, Germany)》2015,21(18):6921-6929
Two small‐molecule–drug conjugates (SMDCs, 6 and 7 ) featuring lysosomally cleavable linkers (namely the Val–Ala and Phe–Lys peptide sequences) were synthesized by conjugation of the αvβ3‐integrin ligand cyclo[DKP–RGD]‐CH2NH2 ( 2 ) to the anticancer drug paclitaxel (PTX). A third cyclo[DKP–RGD]–PTX conjugate with a nonpeptide “uncleavable” linker ( 8 ) was also synthesized to be tested as a negative control. These three SMDCs were able to inhibit biotinylated vitronectin binding to the purified αVβ3‐integrin receptor at nanomolar concentrations and showed good stability at pH 7.4 and pH 5.5. Cleavage of the two peptide linkers was observed in the presence of lysosomal enzymes, whereas conjugate 8 , which possesses a nonpeptide “uncleavable” linker, remained intact under these conditions. The antiproliferative activities of the conjugates were evaluated against two isogenic cell lines expressing the integrin receptor at different levels: the acute lymphoblastic leukemia cell line CCRF‐CEM (αVβ3?) and its subclone CCRF‐CEM αVβ3 (αVβ3+). Fairly effective integrin targeting was displayed by the cyclo[DKP–RGD]–Val–Ala–PTX conjugate ( 6 ), which was found to differentially inhibit proliferation in antigen‐positive CCRF‐CEM αVβ3 versus antigen‐negative isogenic CCRF‐CEM cells. The total lack of activity displayed by the “uncleavable” cyclo[DKP–RGD]–PTX conjugate ( 8 ) clearly demonstrates the importance of the peptide linker for achieving the selective release of the cytotoxic payload. 相似文献
6.
Daniela Babusca Ana Cezarina Morosanu Dan Gheorghe Dimitriu Corina Cheptea 《Molecular Crystals and Liquid Crystals》2020,698(1):87-97
AbstractThree iso-quinolinium ylids are studied by visible electron absorption spectroscopy from the point of view of their interactions with solvent molecules. The quantum mechanical calculations with Spartan 14 Program and solvatochromism of the intramolecular charge transfer visible absorption band of the studied molecules emphasized the prevalence of universal orientation-induction interactions in aprotic solvents and additionally the presence of hydrogen bond between the ylid molecules and the hydroxyl groups of the solvent molecules. The contribution of each type of interactions in the studied solutions is finally established by a multilinear regression applied to solvatochromic data. 相似文献
7.
Daniela Zarzosa-Moreno Christian Avalos-Gmez Luisa Sofía Ramírez-Texcalco Erick Torres-Lpez Ricardo Ramírez-Mondragn Juan Omar Hernndez-Ramírez Jesús Serrano-Luna Mireya de la Garza 《Molecules (Basel, Switzerland)》2020,25(24)
Due to the emergence of multidrug-resistant pathogens, it is necessary to develop options to fight infections caused by these agents. Lactoferrin (Lf) is a cationic nonheme multifunctional glycoprotein of the innate immune system of mammals that provides numerous benefits. Lf is bacteriostatic and/or bactericidal, can stimulate cell proliferation and differentiation, facilitate iron absorption, improve neural development and cognition, promote bone growth, prevent cancer and exert anti-inflammatory and immunoregulatory effects. Lactoferrin is present in colostrum and milk and is also produced by the secondary granules of polymorphonuclear leukocytes, which store this glycoprotein and release it at sites of infection. Lf is also present in many fluids and exocrine secretions, on the surfaces of the digestive, respiratory and reproductive systems that are commonly exposed to pathogens. Apo-Lf (an iron-free molecule) can be microbiostatic due to its ability to capture ferric iron, blocking the availability of host iron to pathogens. However, apo-Lf is mostly microbicidal via its interaction with the microbial surface, causing membrane damage and altering its permeability function. Lf can inhibit viral entry by binding to cell receptors or viral particles. Lf is also able to counter different important mechanisms evolved by microbial pathogens to infect and invade the host, such as adherence, colonization, invasion, production of biofilms and production of virulence factors such as proteases and toxins. Lf can also cause mitochondrial and caspase-dependent regulated cell death and apoptosis-like in pathogenic yeasts. All of these mechanisms are important targets for treatment with Lf. Holo-Lf (the iron-saturated molecule) can contain up to two ferric ions and can also be microbicidal against some pathogens. On the other hand, lactoferricins (Lfcins) are peptides derived from the N-terminus of Lf that are produced by proteolysis with pepsin under acidic conditions, and they cause similar effects on pathogens to those caused by the parental Lf. Synthetic analog peptides comprising the N-terminus Lf region similarly exhibit potent antimicrobial properties. Importantly, there are no reported pathogens that are resistant to Lf and Lfcins; in addition, Lf and Lfcins have shown a synergistic effect with antimicrobial and antiviral drugs. Due to the Lf properties being microbiostatic, microbicidal, anti-inflammatory and an immune modulator, it represents an excellent natural alternative either alone or as adjuvant in the combat to antibiotic multidrug-resistant bacteria and other pathogens. This review aimed to evaluate the data that appeared in the literature about the effects of Lf and its derived peptides on pathogenic bacteria, protozoa, fungi and viruses and how Lf and Lfcins inhibit the mechanisms developed by these pathogens to cause disease. 相似文献
8.
Daniela Cappello Dr. Ryan R. Maar Prof. Dr. Viktor N. Staroverov Prof. Dr. Joe B. Gilroy 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(24):5522-5529
The creation of dimeric boron difluoride complexes of chelating N-donor ligands is a proven strategy for the enhancement of the optoelectronic properties of fluorescent dyes. We report dimers based on the boron difluoride hydrazone (BODIHY) framework, which offer unique and sometimes unexpected substituent-dependent absorption, emission, and electrochemical properties. BODIHY dimers have low-energy absorption bands (λmax=421 to 479 nm, ϵ=17 200 to 39 900 m −1 cm−1) that are red-shifted relative to monomeric analogues. THF solutions of these dimers exhibit aggregation-induced emission upon addition of water, with emission enhancement factors ranging from 5 to 18. Thin films of BODIHY dimers are weakly emissive as a result of the inner-filter effect, attributed to intermolecular π-type interactions. BODIHY dimers are redox-active and display two one-electron oxidation and two one-electron reduction waves that strongly depend on the N-aryl substituents. These properties are rationalized using density-functional theory calculations and X-ray crystallography experiments. 相似文献
9.
Duloxetine (DLX) is a widely used antidepressant drug belonging to the class of selective serotonin and norepinephrine reuptake inhibitors (SNRIs); its efficacy has been demonstrated in the treatment of not only major depressive disorders but also diabetic neuropathic pain, generalized anxiety disorder, fibromyalgia or stress urinary incontinence. It is a chiral substance and is used in therapy in the form of the enantiopure S‐DLX, which is twice as active as R‐DLX. Several methods have been published for the achiral and chiral determination of DLX in pharmaceuticals, biological materials and environmental samples, the majority using liquid chromatography and capillary electrophoresis coupled with different detection techniques (UV detection, fluorescence, mass spectrometry). The aim of the current review is to provide a systematic survey of the analytical techniques used for the determination of DLX from different matrices. 相似文献
10.
Fernando Bento Cunha Karina Torres Pomini Ana Maria de Guzzi Plepis Virgínia da Conceio Amaro Martins Eduardo Gomes Machado Renato de Moraes Marcelo de Azevedo e Souza Munhoz Michela Vanessa Ribeiro Machado Marco Antonio Hungaro Duarte Murilo Priori Alcalde Daniela Vieira Buchaim Rogrio Leone Buchaim Victor Augusto Ramos Fernandes Eliana de Souza Bastos Mazuqueli Pereira Andr Antonio Pelegrine Marcelo Rodrigues da Cunha 《Molecules (Basel, Switzerland)》2021,26(6)
Autologous bone grafts, used mainly in extensive bone loss, are considered the gold standard treatment in regenerative medicine, but still have limitations mainly in relation to the amount of bone available, donor area, morbidity and creation of additional surgical area. This fact encourages tissue engineering in relation to the need to develop new biomaterials, from sources other than the individual himself. Therefore, the present study aimed to investigate the effects of an elastin and collagen matrix on the bone repair process in critical size defects in rat calvaria. The animals (Wistar rats, n = 30) were submitted to a surgical procedure to create the bone defect and were divided into three groups: Control Group (CG, n = 10), defects filled with blood clot; E24/37 Group (E24/37, n = 10), defects filled with bovine elastin matrix hydrolyzed for 24 h at 37 °C and C24/25 Group (C24/25, n = 10), defects filled with porcine collagen matrix hydrolyzed for 24 h at 25 °C. Macroscopic and radiographic analyses demonstrated the absence of inflammatory signs and infection. Microtomographical 2D and 3D images showed centripetal bone growth and restricted margins of the bone defect. Histologically, the images confirmed the pattern of bone deposition at the margins of the remaining bone and without complete closure by bone tissue. In the morphometric analysis, the groups E24/37 and C24/25 (13.68 ± 1.44; 53.20 ± 4.47, respectively) showed statistically significant differences in relation to the CG (5.86 ± 2.87). It was concluded that the matrices used as scaffolds are biocompatible and increase the formation of new bone in a critical size defect, with greater formation in the polymer derived from the intestinal serous layer of porcine origin (C24/25). 相似文献