scholarly journals Synthesis, Anticonvulsant and Antinociceptive Activity of New Hybrid Compounds: Derivatives of 3-(3-Methylthiophen-2-yl)-pyrrolidine-2,5-dione

2020 ◽  
Vol 21 (16) ◽  
pp. 5750
Author(s):  
Małgorzata Góra ◽  
Anna Czopek ◽  
Anna Rapacz ◽  
Anna Dziubina ◽  
Monika Głuch-Lutwin ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Antinociceptive Activity ◽  
Maximal Electroshock ◽  
Hot Plate Test ◽  
Hybrid Compounds ◽  
Mes Test ◽  
Animal Models Of Epilepsy ◽  
New Compounds ◽  
Derivatives Of

The present study aimed to design and synthesize a new series of hybrid compounds with pyrrolidine-2,5-dione and thiophene rings in the structure as potential anticonvulsant and antinociceptive agents. For this purpose, we obtained a series of new compounds and evaluated their anticonvulsant activity in animal models of epilepsy (maximal electroshock (MES), psychomotor (6 Hz), and subcutaneous pentylenetetrazole (scPTZ) seizure tests). To determine the mechanism of action of the most active anticonvulsant compounds (3, 4, 6, 9), their influence on the voltage-gated sodium and calcium channels as well as GABA transporter (GAT) was assessed. The most promising compound 3-(3-methylthiophen-2-yl)-1-(3-morpholinopropyl)pyrrolidine-2,5-dione hydrochloride (4) showed higher ED50 value than those of the reference drugs: valproic acid (VPA) and ethosuximide (ETX) (62.14 mg/kg vs. 252.7 mg/kg (VPA) in the MES test, and 75.59 mg/kg vs. 130.6 mg/kg (VPA) and 221.7 mg/kg (ETX) in the 6 Hz test, respectively). Moreover, in vitro studies of compound 4 showed moderate but balanced inhibition of the neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Additionally, the antinociceptive activity of the most active compounds (3, 4, 6, 9) was also evaluated in the hot plate test and writhing tests, and their hepatotoxic properties in HepG2 cells were also investigated. To determine the possible mechanism of the analgesic effect of compounds 3, 6, and 9, the affinity for the TRPV1 receptor was investigated.

scholarly journals Synthesis, Anticonvulsant, and Antinociceptive Activity of New 3-(2-Chlorophenyl)- and 3-(3-Chlorophenyl)-2,5-dioxo-pyrrolidin-1-yl-acetamides

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1564
Author(s):  
Małgorzata Góra ◽  
Anna Czopek ◽  
Anna Rapacz ◽  
Anna Gębska ◽  
Katarzyna Wójcik-Pszczoła ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Antinociceptive Activity ◽  
Maximal Electroshock ◽  
Reference Drug ◽  
Protective Index ◽  
Mes Test ◽  
Trpv1 Receptors ◽  
Analgesic Agents ◽  
Molecular Mechanism Of Action ◽  
Tonic Pain

The new series of 3-(2-chlorophenyl)- and 3-(3-chlorophenyl)-pyrrolidine-2,5-dione-acetamide derivatives as potential anticonvulsant and analgesic agents was synthesized. The compounds obtained were evaluated in the following acute models of epilepsy: maximal electroshock (MES), psychomotor (6 Hz, 32 mA), and subcutaneous pentylenetetrazole (scPTZ) seizure tests. The most active substance-3-(2-chlorophenyl)-1-{2-[4-(4-fluorophenyl)piperazin-1-yl]-2-oxoethyl}-pyrrolidine-2,5-dione (6) showed more beneficial ED50 and protective index values than the reference drug—valproic acid (68.30 mg/kg vs. 252.74 mg/kg in the MES test and 28.20 mg/kg vs. 130.64 mg/kg in the 6 Hz (32 mA) test, respectively). Since anticonvulsant drugs are often effective in neuropathic pain management, the antinociceptive activity for two the promising compounds—namely, 6 and 19—was also investigated in the formalin model of tonic pain. Additionally, for the aforementioned compounds, the affinity for the voltage-gated sodium and calcium channels, as well as GABAA and TRPV1 receptors, was determined. As a result, the most probable molecular mechanism of action for the most active compound 6 relies on interaction with neuronal voltage-sensitive sodium (site 2) and L-type calcium channels. Compounds 6 and 19 were also tested for their neurotoxic and hepatotoxic properties and showed no significant cytotoxic effect.

scholarly journals Novel Derivatives of 4-Methyl-1,2,3-Thiadiazole-5-Carboxylic Acid Hydrazide: Synthesis, Lipophilicity, and In Vitro Antimicrobial Activity Screening

2021 ◽  
Vol 11 (3) ◽  
pp. 1180
Author(s):  
Kinga Paruch ◽  
Łukasz Popiołek ◽  
Anna Biernasiuk ◽  
Anna Berecka-Rycerz ◽  
Anna Malm ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Carboxylic Acid ◽  
Bacterial Infections ◽  
Acid Hydrazide ◽  
Antimicrobial Effect ◽  
In Vitro Antimicrobial Activity ◽  
Research Goal ◽  
New Compounds ◽  
Derivatives Of

Bacterial infections, especially those caused by strains resistant to commonly used antibiotics and chemotherapeutics, are still a current threat to public health. Therefore, the search for new molecules with potential antimicrobial activity is an important research goal. In this article, we present the synthesis and evaluation of the in vitro antimicrobial activity of a series of 15 new derivatives of 4-methyl-1,2,3-thiadiazole-5-carboxylic acid. The potential antimicrobial effect of the new compounds was observed mainly against Gram-positive bacteria. Compound 15, with the 5-nitro-2-furoyl moiety, showed the highest bioactivity: minimum inhibitory concentration (MIC) = 1.95–15.62 µg/mL and minimum bactericidal concentration (MBC)/MIC = 1–4 µg/mL.

scholarly journals Syntheses and PDT activity of new mono- and di-conjugated derivatives of chlorin e6

2017 ◽  
Vol 21 (04-06) ◽  
pp. 354-363 ◽  
Author(s):  
Hui Chen ◽  
Stewart W. Humble ◽  
R. G. Waruna Jinadasa ◽  
Zehua Zhou ◽  
Alex L. Nguyen ◽  
...  
Keyword(s):  
Amino Acid ◽  
In Vitro Cytotoxicity ◽  
Chlorin E6 ◽  
New Compounds ◽  
Derivatives Of

Syntheses of three new chlorin e6 conjugates for PDT of tumors are reported. One of the new compounds 17 is conjugated with lysine at the 131-position, but the others are mono-conjugated 14 or diconjugated 15 with the non-amino acid species ethanolamine. Cellular experiments with the three new compounds and previously synthesized non-amino acid 152-conjugates (7–10), 131-monoconjugates 14, 16, and a 131,152-diconjugate 12 are reported. In vitro cytotoxicity experiments show that the 131-conjugates are more toxic than the 152-conjugates, and the most toxic derivative (dark- and photo-toxicity) is the 131-ethylenediamine conjugate 11. The most useful PDT photosentitizers appear to be the ethanolamine derivatives, conjugated at the 152- and the 131,152-positions; these show high phototoxicity but relatively low dark toxicity compared with 11, and also the highest dark/photo cytotoxicity ratios.

scholarly journals Synthesis and Antimicrobial Evaluations of Sulfur Inserted Fluoro-Benzimidazoles

2021 ◽  
Vol 33 (7) ◽  
pp. 1525-1529
Author(s):  
Parmesh Kumar Dwivedi ◽  
Devdutt Chaturvedi
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Strains ◽  
Substituted Anilines ◽  
Gram Positive ◽  
Gram Negative ◽  
E Coli ◽  
New Compounds ◽  
Derivatives Of ◽  
Multiple Step

A new series of fluorinated sulfur inserted benzimidazole analogues Za-i were synthesized and characterized. The new compounds were screened for their antimicrobial and antioxidant potential. The synthesized compounds were obtained by multiple step synthesis, initiating from the synthesis of 5-(difluoromethoxy)-1H-benzimidazole-2-thiol X. The compounds Ya-i prepared by reacting differently substituted anilines with chloroacetylchloride and triethylamine in DMF. Finally, the compound X was reacted with different derivatives of 2-chloro-N-phenylacetamide resulting in formation of titled compounds Za-i. The synthesized compounds (Za-Zi) were characterized by spectral analysis viz.1H & 13C NMR, mass spectra, elemental analysis and IR. The in vitro antimicrobial potential against Gram-positive (S. aureus and E. faecalis) and Gram-negative bacterial (E. coli and P.aeruginosa) strains as well as fungi (A. niger and C. albicans) was recorded for the obtained compounds. Some of the compounds exhibited encouraging results (in MIC) against Gram-positive and Gram-negative bacterial strains. These studies thus suggest that the designed sulfur inserted fluoro-benzimidazoles scaffold may serve as new promising template for further amplification as antimicrobial agents.

scholarly journals SYNTHESIS, ANTIAGGREGATION AND ANTITROMBOTIC ACTIVITIES OF NEW DERIVATIVES OF HYDROXYBENZOIC ACIDS WITH TAURIC FRAGMENT

2021 ◽  
Vol 9 (3) ◽  
pp. 222-234
Author(s):  
A. K. Brel ◽  
N. V. Atapina ◽  
Yu. N. Budaeva ◽  
S. V. Lisina ◽  
S. S. Tsaruk ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Acetylsalicylic Acid ◽  
Antiplatelet Activity ◽  
Dipotassium Salt ◽  
Hydroxybenzoic Acids ◽  
New Compounds ◽  
Derivatives Of ◽  
Salt Forms

A high prevalence of thrombotic disorders, insufficient effectiveness or safety of antithrombotic therapy is an urgent problem of modern healthcare. The main means of preventing thrombosis is acetylsalicylic acid. Despite its long history, aspirin attracts researchers in the fields of medicinal chemistry, biology, and medicine. The development of new antiplatelet agents, including chemical modification of the acetylsalicylic acid molecule, remains relevant. Modification of the acetylsalicylic acid molecule using amino acids and obtaining their salt forms makes it possible to maintain antiplatelet or antithrombotic properties, as well as to impart additional pharmacodynamic effects. In modern science, a lot of attention is paid to the sulfur-containing amino acid taurine. An analysis of modern scientific literature revealed the protective effect of taurine in diabetes mellitus and cardiovascular diseases, liver dysfunction, gastrointestinal tract, and kidney diseases.The aim of the article is to study synthesis of new compounds, determination of their physical characteristics and assessment of their antiplatelet and antithrombotic activities in vitro and in vivo.Materials and methods. To confirm the structure of the synthesized new derivatives of hydroxybenzoic acids with a taurine fragment by the acelation method, thin layer chromatography and NMR spectra were used. In vitro studies were carried out on the model of ADP-induced platelet aggregation according to the Born G. methods modified by V.A. Gabbasov. In vivo, the studies were carried out on the model of arterial thrombosis induced by the application of iron chloride in the following groups of animals: intact, with experimental diabetes mellitus and three-year-olds; the rate of bleeding from the tail vein was also evaluated.Results. New compounds – derivatives of ortho-, meta- and para-hydroxybenzoic acids with a taurine residue – were synthesized. A procedure for the preparation of N-hydroxybenzoyl taurine compounds and their salt forms have been described; their spectral characteristics and melting points have been determined. The synthesized compounds are superior to acetylsalicylic acid in solubility and are not inferior to it in antiplatelet and antithrombotic activities. The results of the in vitro antiplatelet activity assessment in a wide concentration range from 10-4M to 10-8M, are presented. It has been revealed that the dipotassium salt of N-(2-hydroxybenzoyl)taurine exhibits a less antiplatelet activity than the dipotassium salt of N-(3-hydroxybenzoyl)taurine. The most pronounced antiplatelet activity is exhibited by the compound N-(4-hydroxybenzoyl)taurine. In in vivo experiments on the model of arterial thrombosis in 3-year-olds or animals with experimental diabetes mellitus, carotid artery thrombosis occurred faster than in young or intact animals. A single preliminary oral administration of the test compounds prolonged the time of the thrombus formation, which makes it possible to conclude that they have an antithrombotic effect. In this study, the dipotassium salt of N-(3-hydroxybenzoyl)taurine exhibits a more pronounced activity than that of acetylsalicylic acid.Conclusion. Against the background of the modeled pathologies, the studied drugs showed the expected antithrombotic activity, in terms of the severity not inferior to that found in acetylsalicylic acid.

scholarly journals Synthesis, characterization and microbial screening of some new methyl 4, 6-o-(4-methoxybenzylidene)-?-D-glucopyranoside Derivatives

2014 ◽  
Vol 37 (2) ◽  
pp. 145-158 ◽  
Author(s):  
Sarkar MA Kawsar ◽  
Abul K MS Kabir ◽  
Mohammad M R Bhuiyan ◽  
Jannatul Ferdous ◽  
Mohammad S Rahman
Keyword(s):  
Pathogenic Bacteria ◽  
Pathogenic Fungi ◽  
Antimicrobial Activities ◽  
Bacterial Strains ◽  
Additional Information ◽  
Fungal Phytopathogens ◽  
New Compounds ◽  
Academy Of Sciences ◽  
Derivatives Of

Regioselective pentanoylation of methyl 4,6-O-(4-methoxybenzylidene)-?-D-glucopyranoside by the direct acylation method provided the methyl 4,6-O-(4-methoxybenzylidene)-2-O-pentanoyl- ?-D-glucopyranoside in good yield. A number of 3-O-acyl derivatives of this 2-O-pentanoylation product were also prepared in order to obtain new compounds and also gather additional information for structure elucidation. The chemical structure of the newly synthesized compounds was characterized by analytical and spectral methods. Synthesized acylated derivatives of Dglucopyranoside were screened for in vitro antimicrobial activities against ten human pathogenic bacteria and four plant pathogenic fungi. The study revealed that the acylated products exhibited moderate to good antimicrobial activities. It was interesting to observe that the selected compounds were more sensitive against fungal phytopathogens than those of the bacterial strains. DOI: http://dx.doi.org/10.3329/jbas.v37i2.17554 Journal of Bangladesh Academy of Sciences, Vol. 37, No. 2, 145-158, 2013

scholarly journals Molecular Structure, In Vitro Anticancer Study and Molecular Docking of New Phosphate Derivatives of Betulin

Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 737
Author(s):  
Elwira Chrobak ◽  
Maria Jastrzębska ◽  
Ewa Bębenek ◽  
Monika Kadela-Tomanek ◽  
Krzysztof Marciniec ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Cell Lines ◽  
Human Cancer ◽  
Amelanotic Melanoma ◽  
Human Cancer Cell Lines ◽  
Ic50 Values ◽  
C 32 ◽  
New Compounds ◽  
Derivatives Of

A series of 30-diethylphosphate derivatives of betulin were synthesized and evaluated for their in vitro cytotoxic activity against human cancer cell lines, such as amelanotic melanoma (C-32), glioblastoma (SNB-19), and two lines of breast cancer (T47D, MDA-MB-231). The molecular structure and activities of the new compounds were also compared with their 29-phosphonate analogs. Compounds 7a and 7b showed the highest activity against C-32 and SNB-19 cell lines. The IC50 values for 7a were 2.15 and 0.91 μM, and, for 7b, they were 0.76 and 0.8 μM for the C-32 and SNB-19 lines, respectively. The most potent compounds, 7a and 7b, were tested for their effects on markers of apoptosis, such as H3, TP53, BAX, and BCL-2. For the whole series of phosphate derivatives, a lipophilicity study was performed, and the ADME parameters were calculated. The most active products were docked to the active site of the EGFR protein. The relative binding affinity of selected phosphate betulin derivatives toward EGFR was compared with standard erlotinib on the basis of ChemScore and KDEEP score. Positively, all derivatives docked inside the cavity and showed significant interactions. Moreover, a molecular dynamics study also reveals that ligands 7a,b form stable complexes and the plateau phase started after 7 ns.

scholarly journals New Coumarinic Azo-Derivatives of Metoclopramide and Diphenhydramine: Synthesis and In Vitro Testing for Cholinesterase Inhibitory Effect and Protection Ability Against Chlorpyrifos

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahmood AAJ ◽  
Mustafa YS ◽  
Abdulstaar M
Keyword(s):  
Inhibitory Effect ◽  
Azo Compounds ◽  
Inhibitory Effects ◽  
High Concentration ◽  
Low Concentrations ◽  
Maximum Protection ◽  
Coumarin Compounds ◽  
New Compounds ◽  
Derivatives Of

Introduction: This study aims to synthesize new coumarin azo compounds of metoclopramide and diphenhydramine and to evaluate their in vitro cholinesterase inhibitory effects and protection abilities against chlorpyrifos. Methods: Two series of azo coumarin compounds were synthesized. Series I compound resulted from the diazotization of metoclopramide and then coupling with coumarin and 4-methyl coumarin to give compounds 1 and 2 respectively. Series II compound resulted from the diazotization of 7-aminocoumarin and 7-amino 4-methyl coumarin and then coupling with diphenhydramine to give compounds 3 and 4 respectively. The new compounds were tested for their in vitro cholinesterase inhibitory effect and protection ability against chlorpyrifos using the modified Elman electrometric method. Results: Metoclopramide derivatives with coumarin show selectivity protection for ChE against chlorpyriphos inhibitory effect as protect BChE and increase the inhibition of the AChE, or the opposite. Conclusion: Diphenhydramine derivatives with coumarin show more protective ability for both BChE and AChE as one of them shows the maximum protection for all concentration. However, the other derivative shows different manner as the low concentrations act as metoclopramide derivatives while the high concentration act as first diphenhydramine derivative (protect both AChE and BChE).

scholarly journals Synthesis of Oxadiazolyl, Pyrazolyl and Thiazolyl Derivatives of Thiophene-2-Carboxamide as Antimicrobial and Anti-HCV Agents

2017 ◽  
Vol 11 (1) ◽  
pp. 38-53 ◽  
Author(s):  
Ola H. Rizk ◽  
Omaima G. Shaaban ◽  
Abeer E. Abdel Wahab
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Activities ◽  
Hcv Rna ◽  
Bacterial Strains ◽  
Low Concentration ◽  
Oxadiazole Derivatives ◽  
Polymerase Chain ◽  
New Compounds ◽  
Derivatives Of

Introduction: Three series of pyrazole, thiazole and 1,3,4-oxadiazole, derivatives were synthesized starting from 5-amino-4-(hydrazinocarbonyl)-3-methylthiophene-2-carboxamide (2). Methods: All compounds were investigated for their preliminary antimicrobial activity. They were proved to exhibit remarkable antimicrobial activity against Pseudomonas aeruginosa with insignificant activity towards Gram positive bacterial strains and fungi. Results: In-vitro testing of the new compounds on hepatitis-C virus (HCV) replication in hepatocellular carcinoma cell line HepG2 infected with the virus utilizing the reverse transcription polymerase chain reaction technique (RT-PCR) generally showed inhibition of the replication of HCV RNA (–) strands at low concentration, while, eight compounds; 3a, 6, 7a, 7b, 9a, 9b, 10a and 11b proved to inhibit the replication of HCV RNA (+) and (–) strands at very low concentration range 0.08-0.36 μg/mL. Conclusion: Compounds 7b and 11b displayed the highest anti-HCV and antimicrobial activities in this study.

scholarly journals The Screening models for antiepileptic drugs: A Review

2021 ◽  
Vol 11 (2-S) ◽  
pp. 175-178
Author(s):  
Pooja Popat Gaikwad ◽  
Vishal S. Adak ◽  
Rajkumar V. Shete
Keyword(s):  
Animal Models ◽  
Antiepileptic Drugs ◽  
Unmet Needs ◽  
Safety Issue ◽  
Ethanolic Extract ◽  
Maximal Electroshock ◽  
Keywords Epilepsy ◽  
Mes Test ◽  
Animal Models Of Epilepsy ◽  
Models Of Epilepsy

Considering the prevalence of epilepsy and the problems associated with currently available antiepileptic drugs like side effects, resistance, safety issue and high cost, herbal medicine with fewer complications could be very appropriate alternative. Therefore in the present study, we have examined the antiepileptic properties of ethanolic extract of leaves in mice using maximal electroshock seizers (MES)test, Pentylenetetrazole (PTZ), induced seizures, strychnine induced convulsion, Isoniazid-induced convulsions, Picrotoxin-induced convulsions, Kainic acid (KA) model etc.There is increased concern on agents for epilepsy disease modification and prevention. To solve these unmet needs, the research scientist must have a thorough knowledge of available animal models of epilepsy so that he can pick up the best model for his research. In this article, we are reviewing the diversity of animal models of epilepsy and their implications in antiepileptic drug discovery. Keywords: Epilepsy, animal model, seizures,

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