scholarly journals Synthesis and Evaluation of Bioactivity of 6-[(2-Pyridinyloxy)](Benzo)Imidazo[2,1-b][1,3]Thiazine Derivatives

2021 ◽  
Vol 12 (4) ◽  
pp. 5031-5044
Keyword(s):  
Antifungal Activity ◽  
The Other ◽  
Albino Rats ◽  
Target Compound ◽  
Mild Conditions ◽  
In Vivo Experiments ◽  
Nmr Spectrometry ◽  
Suppression Index

A series of new 6-[(pyridine-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b]thiazines 4a-l and their benzoannelated derivatives 4m-r was synthesized by the reaction between 3-hydroxy(benzo)imidazo[2,1-b][1,3]thiazines and substituted 2-chloropyridines under the mild conditions with the yield 53-74 %. The structure of the target compound was proven by the results of 1H NMR, 13C NMR spectrometry, and LC-MS. In silico evaluation of these drug-like compounds proved that many of them comply with the Lipinski ‘rule of five’ and the Veber rule. Antibacterial, antifungal, and anti-inflammatory activity of all synthesized compounds were investigated in the in vitro and in vivo experiments. According to the bio screening results, the compounds 6-[(5-сhloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4a, 6-[(3,5-dichloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4e and 6-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}-2,3-diphenyl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4l proved antifungal activity against Candida albicans. On the other hand, 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine 4q proved the best antifungal activity against Aspergillus niger K 9 (MIC=15.62 µg/ml) and comparatively high antiedema activity against the carrageenan-induced edema of the hind paws of albino rats (the inflammation suppression index was 39.1 %).

scholarly journals Antifungal Activity of an Original Amino-Isocyanonaphthalene (ICAN) Compound Family: Promising Broad Spectrum Antifungals

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 903
Author(s):  
Miklós Nagy ◽  
Gábor Szemán-Nagy ◽  
Alexandra Kiss ◽  
Zsolt László Nagy ◽  
László Tálas ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Candida Species ◽  
Fungal Pathogens ◽  
Clinical Strain ◽  
Control Group ◽  
Multiple Drug ◽  
Species Structure ◽  
In Vivo Experiments

Multiple drug resistant fungi pose a serious threat to human health, therefore the development of completely new antimycotics is of paramount importance. The in vitro antifungal activity of the original, 1-amino-5-isocyanonaphthalenes (ICANs) was evaluated against reference strains of clinically important Candida species. Structure-activity studies revealed that the naphthalene core and the isocyano- together with the amino moieties are all necessary to exert antifungal activity. 1,1-N-dimethylamino-5-isocyanonaphthalene (DIMICAN), the most promising candidate, was tested further in vitro against clinical isolates of Candida species, yielding a minimum inhibitory concentration (MIC) of 0.04–1.25 µg/mL. DIMICAN was found to be effective against intrinsically fluconazole resistant Candida krusei isolates, too. In vivo experiments were performed in a severly neutropenic murine model inoculated with a clinical strain of Candida albicans. Daily administration of 5 mg/kg DIMICAN intraperitoneally resulted in 80% survival even at day 13, whereas 100% of the control group died within six days. Based on these results, ICANs may become an effective clinical lead compound family against fungal pathogens.

Measuring the Coagulability of Fibrinogen in Plasma by Isotopic Means

1967 ◽  
Vol 18 (01/02) ◽  
pp. 276-285 ◽  
Author(s):  
E. Regoeczi
Keyword(s):  
In Vitro Studies ◽  
The Other ◽  
Plasma Fibrinogen ◽  
In Vivo Experiments ◽  
Substitution Level ◽  
Reproducible Technique ◽  
Catabolic Rate ◽  
Intracellular Process

Summary1. A simple and reproducible technique for measuring the clottability of plasma fibrinogen using iodinated fibrinogen is described, the coefficient of variance being less than 1 %.2. In vivo experiments in rabbits and monkeys on one hand and in vitro studies with fibrinogens from various species on the other indicated that :a) Aliquots of a fibrinogen preparation iodinated at the same mean substitution level yield practically identical coagulabilities ;b) Aliquots of one labelled preparation when injected into several healthy animals or mixed with their plasmas give equal values for clottability;c) In normal animals, the clottable proportion of the circulating protein-bound radioactivity is at any time a function of the extra/intravascular distribution and of the catabolic rate of fibrinogen relative to the corresponding values of the contaminating labelled protein.3. The significance of the behaviour of the non-clottable protein-bound radioactivities during fibrinogen turnover experiments for the catabolic mechanism is discussed. It is suggested that fibrinogen catabolism is probably an intracellular process.

scholarly journals Antifungal Activity of Some Lactic Acid Bacteria Against Several Soil-borne Fungal Pathogens Isolated from Strawberry Plants

2018 ◽  
Vol 6 (9) ◽  
pp. 1163
Author(s):  
Elif Canpolat ◽  
Müzeyyen Müge Doğaner ◽  
Sibel Derviş ◽  
Çiğdem Ulubaş Serçe
Keyword(s):  
Lactic Acid ◽  
Antifungal Activity ◽  
Lactic Acid Bacteria ◽  
Fungal Pathogens ◽  
Control Method ◽  
Cell Free Supernatant ◽  
In Vivo Experiments ◽  
Soil Borne Fungi

Developing as an alternative plant disease control method by using beneficial microorganisms and their metabolites has gained so much importance in recent years. In this study, the possibilities of using microorganisms which have potential antimicrobial effects on controlling soil-borne fungi at strawberry production were investigated. Effects of different lactic acid bacteria (LAB) strains on the development of several soil-borne fungi were studied in vitro and in vivo. LAB were screened for antifungal activity by using cell free supernatant against Fusarium sp., Rhizoctonia sp., Macrophomina sp., Botrytis sp., Phtopythium sp., Cylindrocarpon sp. and Pestalotiopsis sp. Cell free supernatant of LAB isolates showed promising antifungal activity. In vitro effective strains of LAB were tested in pot experiments to search their effects on disease development and plant growth. While the antifungal effects of all LAB strains tested in vitro experiments exhibited promising results, in vivo experiments revealed similar effects on different fungi genera.

scholarly journals In Vitro and In Vivo Inhibition of Cylindrocladium reteaudii by Essential Oils of Acorus calamus Rhizomes

2020 ◽  
Vol 19 (1) ◽  
pp. 34-42
Author(s):  
Phanin Sintawarak ◽  
◽  
Suwimon Uthairatsamee ◽  
Tharnrat Keawgrajang ◽  
◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Essential Oil ◽  
Essential Oils ◽  
Fungal Growth ◽  
Antifungal Compound ◽  
Acorus Calamus ◽  
In Vivo Experiments ◽  
Oil Concentration

Cylindrocladium reteaudii (Bugnic.) Boesew. is a severe pathogen which can cause leaf blight disease in Eucalyptus seedlings in tropical countries. This study investigated the antifungal activity of essential oils extracted from Acorus calamus L. rhizomes in inhibiting the growth of C. reteaudii, both in in vitro and in vivo experiments. The extraction of essential oils from rhizomes was carried out by hydro-distillation technique and the in vitro antifungal testing was done by using the poisoned food technique. The results indicated that an essential oil concentration of 2,000 ppm can completely inhibit the fungal growth with a 50% inhibitory concentration value of 54.76 ppm. For the in vivo experiment, it was found that an essential oil concentration of 500 ppm and Captan® of 1,000 ppm were not significantly different in inhibiting the growth of C. reteaudii. However, these two treatments significantly inhibited the fungal growth (p<0.05) when compared with the control treatments. Physiological and anatomical characteristics were investigated to check for the antifungal activity after the application of essential oils. Results showed that essential oil spraying had no effect on the leaf transpiration rate and temperature of the Eucalyptus seedlings, but the incident disease ratio was high when an essential oil concentration of more than 1,500 ppm was applied. Therefore, it can be inferred that the essential oils from A. calamus rhizomes at an optimum concentration can be an efficient antifungal compound with a potential to control leaf and shoot blight diseases in Eucalyptus seedlings in a nursery.

scholarly journals Some New Carbacylamidophosphates as Inhibitors of Acetylcholinesterase and Butyrylcholinesterase

2008 ◽  
Vol 63 (3-4) ◽  
pp. 241-250 ◽  
Author(s):  
Khodayar Gholivand ◽  
Ahlam Madani Alizadehgan ◽  
Fresia Mojahed ◽  
Gholamreza Dehghan ◽  
Azadeh Mohammadirad ◽  
...  
Keyword(s):  
General Formula ◽  
Organophosphorus Compounds ◽  
The Other ◽  
Inhibition Activity ◽  
In Vivo Experiments ◽  
Significant Difference ◽  
Inhibition Potency ◽  
Compound Series

The differences in the inhibition activity of organophosphorus agents are a manifestation of different molecular properties of the inhibitors involved in the interaction with the active site of enzyme. We were interested in comparing the inhibition potency of four known synthesized carbacylamidophosphates with the general formula RC(O)NHP(O)Cl2, constituting organophosphorus compounds, where R = CCl3 (1), CHCl2 (2), CH2Cl (3) and CF3 (4), and four new ones with the general formula RC(O)NHP(O)(R′)2, where R′ = morpholine and R = CCl3 (5), CHCl2 (6), CH2Cl (7), CF3 (8), on AChE and BuChE activities. In addition, in vitro activities of all eight compounds on BuChE were determined. Besides, in vivo inhibition potency of compounds 2 and 6, which had the highest inhibition potency among the tested compounds, was studied. The data demonstrated that compound 2 from the compound series 1 to 4 and compound 6 from the compound series 5 to 8 are the most sensitive as AChE and BuChE inhibitors, respectively. Comparing the IC50 values of these compounds, it was clear that the inhibition potency of these compounds for AChE are 2- to 100-fold greater than for BuChE inhibition. Comparison of the kinetics (IC50, Ki, kp, KA and KD) of AChE and BuChE inactivation by these compounds resulted in no significant difference for the measured variables except for compounds 2 and 6, which appeared to be more sensitive to AChE and BuChE by significantly higher kp and Ki values and a lower IC50 value in comparison with the other compounds. The LD50 value of compounds 2 and 6, after oral administration, and the changes of erythrocyte AChE and plasma BuChE activities in albino mice were studied. The in vivo experiments, similar to the in vitro results, showed that compound 2 is a stronger AChE and BuChE inhibitor than the other synthesized carbacylamidophosphates. Furthermore, in this study, the importance of electropositivity of the phosphorus atom, steric hindrance and leaving group specificity were reinforced as important determinants of inhibition activity

Enhancement of ADP-induced Platelet Aggregation by Adrenaline in Vivo and Its Prevention

1973 ◽  
Vol 29 (02) ◽  
pp. 490-498 ◽  
Author(s):  
Hiroh Yamazaki ◽  
Itsuro Kobayashi ◽  
Tadahiro Sano ◽  
Takio Shimamoto
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
The Other ◽  
Endothelial Surface ◽  
Important Interaction ◽  
Blood Coagulability ◽  
The Difference

SummaryThe authors previously reported a transient decrease in adhesive platelet count and an enhancement of blood coagulability after administration of a small amount of adrenaline (0.1-1 µg per Kg, i. v.) in man and rabbit. In such circumstances, the sensitivity of platelets to aggregation induced by ADP was studied by an optical density method. Five minutes after i. v. injection of 1 µg per Kg of adrenaline in 10 rabbits, intensity of platelet aggregation increased to 115.1 ± 4.9% (mean ± S. E.) by 10∼5 molar, 121.8 ± 7.8% by 3 × 10-6 molar and 129.4 ± 12.8% of the value before the injection by 10”6 molar ADP. The difference was statistically significant (P<0.01-0.05). The above change was not observed in each group of rabbits injected with saline, 1 µg per Kg of 1-noradrenaline or 0.1 and 10 µg per Kg of adrenaline. Also, it was prevented by oral administration of 10 mg per Kg of phenoxybenzamine or propranolol or aspirin or pyridinolcarbamate 3 hours before the challenge. On the other hand, the enhancement of ADP-induced platelet aggregation was not observed in vitro, when 10-5 or 3 × 10-6 molar and 129.4 ± 12.8% of the value before 10∼6 molar ADP was added to citrated platelet rich plasma (CPRP) of rabbit after incubation at 37°C for 30 second with 0.01, 0.1, 1, 10 or 100 µg per ml of adrenaline or noradrenaline. These results suggest an important interaction between endothelial surface and platelets in connection with the enhancement of ADP-induced platelet aggregation by adrenaline in vivo.

ANTITUMOR EFFECT OF COLLOIDAL SILVER BISILICATE IN EXPERIMENTAL IN VITRO AND IN VIVO STUDIES

2019 ◽  
Vol 65 (5) ◽  
pp. 760-765
Author(s):  
Margarita Tyndyk ◽  
Irina Popovich ◽  
A. Malek ◽  
R. Samsonov ◽  
N. Germanov ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Tumor Growth ◽  
Tumor Cells ◽  
Human Tumor ◽  
Significant Inhibition ◽  
In Vivo Studies ◽  
Ehrlich Carcinoma ◽  
In Vivo Experiments

The paper presents the results of the research on the antitumor activity of a new drug - atomic clusters of silver (ACS), the colloidal solution of nanostructured silver bisilicate Ag6Si2O7 with particles size of 1-2 nm in deionized water. In vitro studies to evaluate the effect of various ACS concentrations in human tumor cells cultures (breast cancer, colon carcinoma and prostate cancer) were conducted. The highest antitumor activity of ACS was observed in dilutions from 2.7 mg/l to 5.1 mg/l, resulting in the death of tumor cells in all studied cell cultures. In vivo experiments on transplanted Ehrlich carcinoma model in mice consuming 0.75 mg/kg ACS with drinking water revealed significant inhibition of tumor growth since the 14th day of experiment (maximally by 52% on the 28th day, p < 0.05) in comparison with control. Subcutaneous injections of 2.5 mg/kg ACS inhibited Ehrlich's tumor growth on the 7th and 10th days of the experiment (p < 0.05) as compared to control.

Synthesis, Characterization and in vivo Evaluation of PEGylated PPI Dendrimer for Safe and Prolonged Delivery of Insulin

2019 ◽  
Vol 9 (3) ◽  
pp. 248-263 ◽  
Author(s):  
Ashish K. Parashar ◽  
Preeti Patel ◽  
Arun K. Gupta ◽  
Neetesh K. Jain ◽  
Balak Das Kurmi
Keyword(s):  
Blood Glucose ◽  
Drug Release ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Albino Rats ◽  
Sustained Delivery ◽  
In Vivo Evaluation ◽  
Hemolytic Toxicity

Background: The present study was aimed at developing and exploring the use of PEGylated Poly (propyleneimine) dendrimers for the delivery of an anti-diabetic drug, insulin. Methods: For this study, 4.0G PPI dendrimer was synthesized by successive Michael addition and exhaustive amidation reactions, using ethylenediamine as the core and acrylonitrile as the propagating agent. Two different activated PEG moieties were employed for PEGylation of PPI dendrimers. Various physicochemical and physiological parameters UV, IR, NMR, TEM, DSC, drug entrapment, drug release, hemolytic toxicity and blood glucose level studies of both PEGylated and non- PEGylated dendritic systems were determined and compared. Results: PEGylation of PPI dendrimers caused increased solubilization of insulin in the dendritic framework as well as in PEG layers, reduced drug release and hemolytic toxicity as well as increased therapeutic efficacy with reduced side effects of insulin. These systems were found to be suitable for sustained delivery of insulin by in vitro and blood glucose-level studies in albino rats, without producing any significant hematological disturbances. Conclusion: Thus, surface modification of PPI dendrimers with PEG molecules has been found to be a suitable approach to utilize it as a safe and effective nano-carrier for drug delivery.

Oxytocin analogues with non-coded amino acid residues in position 8: [8-Neopentylglycine]oxytocin and [8-cycloleucine]oxytocin

1987 ◽  
Vol 52 (9) ◽  
pp. 2317-2325 ◽  
Author(s):  
Jan Hlaváček ◽  
Jan Pospíšek ◽  
Jiřina Slaninová ◽  
Walter Y. Chan ◽  
Victor J. Hruby
Keyword(s):  
Amino Acid ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
The Other ◽  
Amino Acid Residues ◽  
Phase Synthesis ◽  
Other Hand ◽  
Fragment Condensation

[8-Neopentylglycine]oxytocin (II) and [8-cycloleucine]oxytocin (III) were prepared by a combination of solid-phase synthesis and fragment condensation. Both analogues exhibited decreased uterotonic potency in vitro, each being about 15-30% that of oxytocin. Analogue II also displayed similarly decreased uterotonic potency in vivo and galactogogic potency. On the other hand, analogue III exhibited almost the same potency as oxytocin in the uterotonic assay in vivo and in the galactogogic assay.

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