scholarly journals Еvaluation of antitumor activity of some 4-aminopiperidine derivatives — low molecular weight Hsp70 inhibitors — on transplantable mouse tumors

2021 ◽  
Author(s):  
VN Aldobaev ◽  
LV Mikhina ◽  
MA Present
Keyword(s):  
Molecular Weight ◽  
Antitumor Activity ◽  
Therapeutic Potential ◽  
B16 Melanoma ◽  
Lymphocytic Leukemia ◽  
Low Molecular Weight ◽  
L1210 Leukemia ◽  
In Vivo Models ◽  
Hsp70 Inhibitors

Low molecular weight compounds targeting chaperone proteins Hsp90 and Hsp70 have opened up a new avenue in the therapy of neoplasms. In 2020, we tested 3 Hsp70 inhibitors from the class of 4-aminopiperidine derivatives for their antitumor activity on in vivo models. The list of the tested compounds included N-(2-chlorobenzyl)-N-ethyl-1-(2-(methylthio)pyrimidin-4-yl)piperidin-4-amine (compound 1), 4-((methyl(1-(2-(methylthio)pyrimidin-4-yl) piperidin-4-yl)amino)methyl) benzonitrile (compound 2) and N-(2,6- dichlorobenzyl)-1-(1-(2-(ethylthio)pyrimidin-4-yl)piperidin-4-yl)-N-methylmethaneamine (compound 3). The aim of this study was to compare the efficacy of 4-aminopiperidine derivatives in vivo using the models of transplantable murine L1210 lymphocytic leukemia and B16 melanoma. Compounds 2 and 3 used in combination with cyclophosphamide exhibited high cytotoxic activity (р = 0.05) against L1210 leukemia (an 80-82% increase in survival time) and B16 melanoma (98-99.7% tumor growth delay). For L1210 lymphocytic leukemia, compounds 2 and 3 used in combination with cyclophosphamide fell into the low (+) therapeutic potential category. For B16 melanoma, compounds 1, 2 and 3 used in combination with cyclophosphamide fell into either low (+) or moderate (++) therapeutic potential categories. On the whole, the tested doses of the compounds used in combination with cyclophosphamide hold promise for the therapy of L1210 leukemia and B16 melanoma in mouse models. Our findings confirm the potential of low molecular weight Hsp70 inhibitors for combination chemotherapy against cancer.

scholarly journals In vitroandin vivo antibacterial activities of rhizophora man-gle l. against helicobacter pylori. chemical compounds elucida-tion

2017 ◽  
Vol 5 (1) ◽  
pp. 31
Author(s):  
Sánchez Perera Luz María ◽  
Morales Espinosa María Rosario ◽  
Delgado Lamas Guillermo ◽  
De Mendonça Sergio ◽  
Cortes Diego Miguel ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Helicobacter Pylori ◽  
Aqueous Extract ◽  
Antibacterial Activities ◽  
Active Principle ◽  
Low Molecular Weight ◽  
Total Extract ◽  
In Vivo Models

Rhizophora mangle L. is a vegetal species widely distributed in Cuba and other Caribbean countries with ethno- pharmacology relevance and preview reports as antiulcer and wound healing properties. The present work describes the in vitro and in vivo antibacterial activities of dried aqueous extract of bark and polyphenol fractions from R. mangle against Helicobacter pylori and the identification of new compounds in the active extracts. Minimum inhibitory concentration (MIC) and Minimum bactericide concentration (MBC) were evaluated against reference and clinical Helicobacter pylori strains with total extract, High Molecular Weight and Low Molecular Weight fractions isolated from total extract. Positive active fractions in vitro tests were evaluated in vivo using H. pylori C57BL/6 mice. Fractionation, isolation and structural elucidation of the compounds on High Molecular Weigh fraction and on Low Molecular Weight fraction were made using Chromatography methods and Mass and H+NMR spectrometry. Total aqueous extract from bark of R. mangle and some fraction shown promissory antibacterial activity on in vitro and in vivo models. It was isolated and identified proantocyanidin, catechin and epicatechin derivates, cyanidin and other compounds in this promissory extract. These results appoint to total extract with a promissory active principle in the development of phytodrug with antibacterial effect and as proton pump inhibitor by the treatment of gastroduodenal ulcer.

Antitumor Activity and Mechanism in vivo of Low- Molecular Weight Polysaccharides from Ganoderma lucidum

2010 ◽  
Vol 8 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Fang-Hua HUANG ◽  
Ming-Hong SHANG ◽  
Ya-Ting XIONG ◽  
Jing ZHANG ◽  
Lu-Yong ZHANG
Keyword(s):  
Molecular Weight ◽  
Antitumor Activity ◽  
Ganoderma Lucidum ◽  
Low Molecular Weight

A Low Molecular Weight Polysaccharide Isolated from Agaricus blazei Murill (LMPAB) Exhibits Its Anti-Metastatic Effect by Down-Regulating Metalloproteinase-9 and Up-Regulating Nm23-H1

2009 ◽  
Vol 37 (05) ◽  
pp. 909-921 ◽  
Author(s):  
Ying-Cai Niu ◽  
Ji-Cheng Liu ◽  
Xue-Mei Zhao ◽  
Jun Cao
Keyword(s):  
Molecular Weight ◽  
Cancer Metastasis ◽  
B16 Melanoma ◽  
Low Molecular Weight ◽  
Mouse Tumor ◽  
Agaricus Blazei ◽  
Matrigel Invasion ◽  
Metalloproteinase 9 ◽  
Agaricus Blazei Murill

The components of Agaricus blazei Murill (AbM) have been shown to possess antitumor potentials. Herein, we attempted to explore the anti-metastatic effect and underlying mechanism of a low molecular weight polysaccharide isolated from AbM (LMPAB). Matrigel invasion assay was applied to evaluate the effect of LMPAB on migration of BEL-7402 hepatic cancer cells in vitro. In vivo, the anti-metastatic effect of LMPAB was investigated in mouse B16 melanoma and a double-grafted SW180 tumor models. mRNA and protein levels of metalloproteinase-9 (MMP-9) or nm23-H1 upon LMPAB treatment were detected by real-time PCR and immunohistochemistry assays. LMPAB significantly reduced the invasion of BEL-7402 cells. In vivo, LMPAB was revealed to decrease lung metastatic foci in mouse B16 melanoma model. In the double-grafted SW180 mouse tumor model, we further demonstrated that intratumoral treatment of LMPAB inhibited the growth of tumor on treated side but also suppresses the regression of metastatic tumors on the non-treated side. Moreover, LMPAB reduced MMP-9 but enhanced nm23-H1 mRNA and protein expression. LMPAB displays anti-metastatic activities, indicating the potential of its clinical application for the prevention and treatment of cancer metastasis. Its anti-metastatic effect may relate to the modulation on MMP-9 and nm23-H1.

Effects of Unfractionated and Low Molecular Weight Heparins on Platelet Thromboxane Biosynthesis “In Vivo”

1994 ◽  
Vol 72 (06) ◽  
pp. 942-946 ◽  
Author(s):  
Raffaele Landolfi ◽  
Erica De Candia ◽  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Armando Antinori ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Unfractionated Heparin ◽  
Low Molecular Weight Heparin ◽  
Primary Source ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
Heparin Administration ◽  
To Receive

SummarySeveral “in vitro” and “in vivo” studies indicate that heparin administration may affect platelet function. In this study we investigated the effects of prophylactic heparin on thromboxane (Tx)A2 biosynthesis “in vivo”, as assessed by the urinary excretion of major enzymatic metabolites 11-dehydro-TxB2 and 2,3-dinor-TxB2. Twenty-four patients who were candidates for cholecystectomy because of uncomplicated lithiasis were randomly assigned to receive placebo, unfractionated heparin, low molecular weight heparin or unfractionaed heparin plus 100 mg aspirin. Measurements of daily excretion of Tx metabolites were performed before and during the treatment. In the groups assigned to placebo and to low molecular weight heparin there was no statistically significant modification of Tx metabolite excretion while patients receiving unfractionated heparin had a significant increase of both metabolites (11-dehydro-TxB2: 3844 ± 1388 vs 2092 ±777, p <0.05; 2,3-dinor-TxB2: 2737 ± 808 vs 1535 ± 771 pg/mg creatinine, p <0.05). In patients randomized to receive low-dose aspirin plus unfractionated heparin the excretion of the two metabolites was largely suppressed thus suggesting that platelets are the primary source of enhanced thromboxane biosynthesis associated with heparin administration. These data indicate that unfractionated heparin causes platelet activation “in vivo” and suggest that the use of low molecular weight heparin may avoid this complication.

In Vivo Studies on the Inhibition of Coagulation by Fractionated Heparin and by a Heparin Analogue I. Effects of Heparin Fractions

1981 ◽  
Vol 46 (03) ◽  
pp. 612-616 ◽  
Author(s):  
U Schmitz-Huebner ◽  
L Balleisen ◽  
F Asbeck ◽  
J van de Loo
Keyword(s):  
Molecular Weight ◽  
Day Treatment ◽  
Gel Filtration ◽  
Weight Fraction ◽  
In Vivo Studies ◽  
Low Molecular Weight ◽  
High Molecular Weight Fraction ◽  
Platelet Factor ◽  
Heparin Fractions

SummaryHigh and low molecular weight heparin fractions obtained by gel filtration chromatography of sodium mucosal heparin were injected subcutaneously into six healthy volunteers and compared with the unfractionated substance in a cross-over trial. Equal doses of 5,000 U were administered twice daily over a period of three days and heparin activity was repeatedly controlled before and 2, 4, 8 hrs after injection by means of the APTT, the anti-Xa clotting test and a chromogenic substrate assay. In addition, the in vivo effect of subcutaneously administered fractionated heparin on platelet function was examined on three of the volunteers. The results show that s.c. injections of the low molecular weight fraction induced markedly higher anti-Xa activity than injections of the other preparations. At the same time, APTT results did not significantly differ. Unfractionated heparin and the high molecular weight fraction enhanced ADP-induced platelet aggregation and collagen-mediated MDA production, while the low molecular weight fraction hardly affected these assays, but potently inhibited thrombin-induced MDA production. All heparin preparations stimulated the release of platelet Factor 4 in plasma. During the three-day treatment periods, no side-effects and no significant changes in the response to heparin injections were detected.

Neutralization of a Low Molecular Weight Heparin (LHN-1) and Conventional Heparin by Protamine Sulfate in Rats

1986 ◽  
Vol 56 (03) ◽  
pp. 318-322 ◽  
Author(s):  
V Diness ◽  
P B Østergaard
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Thrombus Formation ◽  
Experimental Models ◽  
Protamine Sulfate ◽  
Low Molecular Weight ◽  
Antithrombotic Effect ◽  
Higher Doses

SummaryThe neutralization of a low molecular weight heparin (LHN-1) and conventional heparin (CH) by protamine sulfate has been studied in vitro and in vivo. In vitro, the APTT activity of CH was completely neutralized in parallel with the anti-Xa activity. The APTT activity of LHN-1 was almost completely neutralized in a way similar to the APTT activity of CH, whereas the anti-Xa activity of LHN-1 was only partially neutralized.In vivo, CH 3 mg/kg and LHN-1 7.2 mg/kg was given intravenously in rats. The APTT and anti-Xa activities, after neutralization by protamine sulfate in vivo, were similar to the results in vitro. In CH treated rats no haemorrhagic effect in the rat tail bleeding test and no antithrombotic effect in the rat stasis model was found at a protamine sulfate to heparin ratio of about 1, which neutralized APTT and anti-Xa activities. In LHN-1 treated rats the haemorrhagic effect was neutralized when APTT was close to normal whereas higher doses of protamine sulfate were required for neutralization of the antithrombotic effect. This probably reflects the fact that in most experimental models higher doses of heparin are needed to induce bleeding than to prevent thrombus formation. Our results demonstrate that even if complete neutralization of APTT and anti-Xa activities were not seen in LHN-1 treated rats, the in vivo effects of LHN-1 could be neutralized as efficiently as those of conventional heparin. The large fall in blood pressure caused by high doses of protamine sulfate alone was prevented by the prior injection of LHN-1.

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