scholarly journals Water-Soluble Cuprizone Derivative: Synthesis, Characterization, and in Vitro Studies

ACS Omega ◽  
2019 ◽  
Vol 4 (1) ◽  
pp. 1685-1689 ◽  
Author(s):  
Martin Fries ◽  
Meike Mertens ◽  
Nico Teske ◽  
Markus Kipp ◽  
Cordian Beyer ◽  
...  
Keyword(s):  
Water Soluble ◽  
In Vitro Studies

Water-soluble octahedral molybdenum cluster compounds Na2[Mo6I8(N3)6] and Na2[Mo6I8(NCS)6]: Syntheses, luminescence, and in vitro studies

2016 ◽  
Vol 441 ◽  
pp. 42-49 ◽  
Author(s):  
Kaplan Kirakci ◽  
Pavel Kubát ◽  
Monika Kučeráková ◽  
Václav Šícha ◽  
Helena Gbelcová ◽  
...  
Keyword(s):  
Water Soluble ◽  
In Vitro Studies ◽  
Cluster Compounds ◽  
Molybdenum Cluster

scholarly journals Identification of New Compounds with Anticonvulsant and Antinociceptive Properties in a Group of 3-substituted (2,5-dioxo-pyrrolidin-1-yl)(phenyl)-Acetamides

2021 ◽  
Vol 22 (23) ◽  
pp. 13092
Author(s):  
Michał Abram ◽  
Marcin Jakubiec ◽  
Anna Rapacz ◽  
Szczepan Mogilski ◽  
Gniewomir Latacz ◽  
...  
Keyword(s):  
Water Soluble ◽  
Calcium Currents ◽  
In Vitro Studies ◽  
Maximal Electroshock ◽  
Induction Effect ◽  
Potential Candidate ◽  
Seizure Models ◽  
Seizure Model

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.

scholarly journals Effect of folic acid on animal models, cell cultures, and human oral clefts: a literature review

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Zita C. Bendahan ◽  
Lina M. Escobar ◽  
Jaime E. Castellanos ◽  
María C. González-Carrera
Keyword(s):  
Folic Acid ◽  
Animal Models ◽  
Protective Effect ◽  
Cleft Lip And Palate ◽  
Cell Types ◽  
Water Soluble ◽  
In Vitro Studies ◽  
Main Body ◽  
Different Cell Types

Abstract Background Folate is a naturally occurring, water-soluble B vitamin. The synthetic form of this compound is folic acid (FA), the deficiency of which is linked to neural tube disorders (NTD), which can be prevented by consuming it before, or during the early months of, pregnancy. However, the effect of FA on oral cleft formation remains controversial. The aim of the present study was to review the evidence concerning the effect of FA on the formation of cleft lip and palate (CLP) in both animals and humans, as well as its impact on different cell types. A search was conducted on various databases, including MEDLINE, EMBASE, and Central, for articles published until January 2020. Main body Current systematic reviews indicate that FA, alone or in combination with other vitamins, prevents NTD; however, there is no consensus on whether its consumption can prevent CLP formation. Conversely, the protective effect of FA on palatal cleft (CP) induction has been inferred from animal models; additionally, in vitro studies enumerate a cell-type and dose-dependent effect of FA on cell viability, proliferation, and differentiation, hence bolstering evidence from epidemiological studies. Conclusions Meta-analysis, animal models, and in vitro studies demonstrated the protective effect of FA against isolated CP; however, the heterogeneity of treatment protocols, doses, and FA administration method, as well as the different cell types used in in vitro studies, does not conclusively establish whether FA prevents CLP formation.

A Novel Orally Available Parthenolide Analog Selectively Eradicates AML Stem and Progenitor Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 237-237 ◽  
Author(s):  
Monica L. Guzman ◽  
Randall M. Rossi ◽  
Xiaojie Li ◽  
Cheryl Corbett ◽  
Duane C. Hassane ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Stress Responses ◽  
Water Solubility ◽  
Blast Crisis ◽  
Scid Mice ◽  
Water Soluble ◽  
In Vitro Studies ◽  
Average Cell ◽  
Stem And Progenitor Cells

Abstract We have previously demonstrated that Parthenolide (PTL), the principal component of the medicinal plant Feverfew, selectively induces apoptosis in AML stem cells while sparing normal counterparts. Recent reports show that PTL is also effective against CLL cells. Additionally, we observed PTL efficacy for ALL cells in vitro. These findings suggest that PTL-derived drugs may provide a unique means of leukemia therapy. A clinical study using Feverfew showed PTL plasma levels were not sufficient to achieve the concentration needed for AML targeting as established by our in vitro studies. Therefore, we synthesized a family of PTL derivatives designed to be more water-soluble. An amino analog, LC-1, retained the anti-leukemia properties of PTL with 1000× improved water solubility. In vitro studies indicate that LC-1 induces irreversible apoptosis of primary human AML cells within 8 h of treatment. Analysis of phenotypically primitive cells (CD34+CD38−, n=27) treated with 5.0–7.5 uM LC-1 for 18–24 h demonstrated an average cell kill of 85–90%. In contrast, normal CD34+CD38− cells showed less than 10% death under the same conditions. Similarly, colony-forming potential of AML specimens (n=5) was inhibited by >90% but by <20% for normal specimens (n=5). Further, engraftment of NOD/SCID mice was reduced by 91% for primary AML specimens (n=3), but only 28% for normal controls. Taken together, these data indicate LC-1 is a potent and selective agent for ablation of primitive AML cells. Moreover, we observed that similar concentrations of LC-1 were effective in ablating blast crisis CML (n=13) and ALL (n=7) specimens, for both total and phenotypically primitive cells. Molecular studies demonstrate that LC-1 induces a strong oxidative stress response characterized by rapid up-regulation of Nrf2 and its downstream target HO-1, followed by p53 activation and NF-kB inhibition. Thus, activation of stress responses and concomitant inhibition of survival mechanisms are evident for LC-1 treated AML cells, and represent potential biomarkers for drug activity. Pharmacodynamic studies of NOD/SCID mice 8 wks after transplantation with primary human AML cells indicate that oral dosing of LC-1 (50–100mg/kg) mediates a clear biological response. Microscopy studies show induction of Nrf2 and HO-1 in transplanted human AML cells within 1 h of treatment, while strong NF-kB inhibition is evident within 2 h. Finally, we also examined the activity of LC-1 for spontaneous acute canine leukemia. In vitro treatment of primary canine leukemia cells (n=4) with 7.5 uM LC-1 resulted in 80% apoptosis. Further, in a case study, a dog with advanced disease was treated for 3 consecutive days with increasing oral doses of LC-1 (25, 50, and 100 mg/kg). Within 5 days of the last treatment, CD34+ tumor cells were reduced from 45% to 3% of circulating WBCs. Thus, the animal demonstrated a clear hematologic response to LC-1 treatment. Based on these findings, we propose that LC-1 may be appropriate for future therapeutic regimens and has the potential to selectively target leukemic stem and progenitor cells in vivo.

Sign in / Sign up

Export Citation Format

Share Document