Synthesis and Anticonvulsant Activity of α-Amino Acid Amide Derivatives

2019 ◽  
Vol 15 (5) ◽  
pp. 547-561
Author(s):  
Valerie Currier ◽  
Maryam Molki ◽  
Katelyn Fryman ◽  
Lacey D. Rodgers ◽  
A. Michael Crider
Keyword(s):  
Amino Acid ◽  
Side Effects ◽  
Anticonvulsant Activity ◽  
Acid Amide ◽  
New Drugs ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Maximal Electroshock Seizure Test ◽  
Amide Derivatives

Background: Epilepsy is a disease of the central nervous system that affects approximately 50 million individuals worldwide. Although several new drugs have been marketed in the last 25 years, almost one-third of patients are not protected. In many cases, currently available drugs produce undesirable side effects. As a result, a need exists for novel anticonvulsants with unique mechanisms of action and minimal side effects. Methods: A mixed anhydride coupling procedure and standard deprotection procedures were utilized to prepare 36 α-amino acid amides. All final products were evaluated in mice and rats utilizing a standard battery of anticonvulsant tests. Results: α-Amino acids containing a 2,6-dimethylanilide group exhibited anticonvulsant activity in the maximal electroshock seizure test and 6 Hz test in mice and rats. A small, branched-chain on the α- carbon generally maintained or enhanced anticonvulsant activity in the maximal electroshock seizure test. The (R)-α-amino acid amides were typically more potent and slightly more neurotoxic than the corresponding (S)-enantiomers. The valine dimethylanilide (R)-42 was highly active in the MES test in mice (ED50 = 3.6mg/kg) and rats (ED50 = 3.8 mg/kg). (R)-42 also demonstrated excellent anticonvulsant activity in the 6 Hz, picrotoxin, and corneal kindled mouse tests. Furthermore, (R)-42 did not lower seizure threshold when evaluated in the intravenous metrazol seizure test. Conclusion: α-Amino acid 2,6-dimethylanilides exhibited potent activity in a variety of anticonvulsant tests in mice and rats. The valine derivative (R)-42 represents a promising compound for potential use in complex partial seizures.

scholarly journals Design, synthesis and anticonvulsant-analgesic activity of new N-[(phenoxy)alkyl]- and N-[(phenoxy)ethoxyethyl]aminoalkanols

MedChemComm ◽  
2017 ◽  
Vol 8 (1) ◽  
pp. 220-238 ◽  
Author(s):  
Anna Rapacz ◽  
Anna M. Waszkielewicz ◽  
Katarzyna Pańczyk ◽  
Karolina Pytka ◽  
Paulina Koczurkiewicz ◽  
...  
Keyword(s):  
Analgesic Activity ◽  
Anticonvulsant Activity ◽  
Seizure Threshold ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Design Synthesis ◽  
Electroshock Seizure Threshold

New aminoalkanols have been synthesized and evaluated for their anticonvulsant activity in maximal electroshock (MES), maximal electroshock seizure threshold (MEST) and pentylenetetrazol (PTZ) tests, and show promising activity.

N-(Fluorenyl-9-methoxycarbonyl)amino Acid Amide Derivatives as a New Class of Anti-cancer Agents

2009 ◽  
pp. 465-466 ◽  
Author(s):  
Lajos Gera ◽  
Daniel C. Chan ◽  
Vitalija Simkeviciene ◽  
Paul A. Jr Bunn ◽  
John M. Stewart
Keyword(s):  
Amino Acid ◽  
Acid Amide ◽  
Amino Acid Amide ◽  
New Class ◽  
Amide Derivatives ◽  
Anti Cancer

scholarly journals Topography of nucleic acid helices in solutions. The interaction specificities of optically active amino acid derivatives

1970 ◽  
Vol 117 (2) ◽  
pp. 247-256 ◽  
Author(s):  
Edmond J. Gabbay ◽  
Roberta W. Kleinman
Keyword(s):  
Amino Acid ◽  
Dissociation Constants ◽  
Acid Amide ◽  
Ion Exchange Resin ◽  
Calf Thymus Dna ◽  
Random Coil ◽  
Amide Derivatives ◽  
Calf Thymus ◽  
Proline Derivatives ◽  
Polar Substituents

The synthesis and interactions of the d- and l-enantiomers of the amino acid amide derivatives [Formula: see text] (I) and lysyl dipeptides [Formula: see text] (II) with poly rI·poly rC, poly rA·poly rU and calf thymus DNA is reported. The following results were found. (1) The degree of stabilization of the helices as measured by the Tm (‘melting’ temperature) of the helix–coil transition was dependent on the nature of the amino acid. (2) For the poly rI·poly rC helix, the l-enantiomers of salts (I) and (II) stabilized more than the d-enantiomers. The same was true for calf thymus DNA in the presence of salts (II) and for poly rA·poly rU in the presence of salts (II) and the proline derivatives of salts (I). (3) As R increased in size and became more apolar, the amount of stabilization of the poly rI·poly rC helix in the presence of salts (I) decreased. On the other hand, the amount of stabilization increased with more polar substituents. An attempt was then made to determine whether the difference in stabilization of the double-stranded helices at the Tm in the presence of the l- and d-enantiomers of salts (I) is due to the interaction with the helix, the random coil or both. A new method was developed for determining the binding of small ions to polyions that involves a competition between an insoluble polystyrene ion-exchange resin and the soluble polyion for the counterion. Dissociation constants are obtained for the complexes of single- and double-stranded helices with the salts (I). The results are illuminating and indicate that with certain helices, i.e. poly rA·poly rU, the interactions of salts (I) with the single strands may not be ignored. It is concluded that the high optical specificity found in Nature, i.e. d-ribose in nucleic acids and l-amino acids in proteins, cannot be attributed solely to monomer–polymer interactions described by Gabbay (1968).

Amino acid amide derivatives of 2-[3-(aminomethyl)-4H-1,2,4-triazol-4-yl]benzophenones, a novel class of annulated peptidoaminobenzophenones

1982 ◽  
Vol 25 (12) ◽  
pp. 1466-1473 ◽  
Author(s):  
Kentaro Hirai ◽  
Toshio Fujishita ◽  
Teruyuki Ishiba ◽  
Hirohiko Sugimoto ◽  
Shigeru Matsutani ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Amide ◽  
Amino Acid Amide ◽  
Amide Derivatives ◽  
Derivatives Of

Evaluation of the Anticonvulsant Activity of Terpinen-4-ol

2009 ◽  
Vol 64 (1-2) ◽  
pp. 1-5 ◽  
Author(s):  
Damião P. de Sousa ◽  
Franklin F. F. Nóbrega ◽  
Liana C. S. L. de Morais ◽  
Reinaldo N. de Almeida
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Animal Models ◽  
Motor Activity ◽  
Anticonvulsant Activity ◽  
Maximal Electroshock ◽  
Aromatic Plants ◽  
Depressant Effect ◽  
Maximal Electroshock Seizure ◽  
The Central Nervous System

Terpinen-4-ol is a monoterpenoid alcohol and component of the essential oils of several aromatic plants. Similarly to terpinen-4-ol, other monoterpenoid alcohols have shown anticonvulsant activity in convulsion animal models. The present study aimed to investigate the anticonvulsant activity of terpinen-4-ol. Treatment of mice with terpinen-4-ol ( 200 mg/kg) caused a signifi cant decrease in the spontaneous motor activity at 30, 60 and 120 min after administration. Terpinen-4-ol (100 and 200 mg/kg) produced a significant dosedependent increase in the duration of sleeping in mice. Pretreatment of mice with terpinen-4- ol at doses of 100, 200 and 300 mg/kg significantly increased the latency of pentylenetetrazole -induced convulsions. Terpinen-4-ol (200 and 300 mg/kg) also inhibited the induced seizures of picrotoxin. In another model, maximal electroshock seizure, terpinen-4-ol decreased the tonic hind convulsions percentage at the dose of 300 mg/kg. From the overall results we can conclude that terpinen-4-ol showed a depressant effect on the central nervous system and significant anticonvulsant activity.

scholarly journals Fluoxetine enhances maximal electroshock seizure threshold in Albino rat model when compared to phenytoin

2017 ◽  
Vol 7 (1) ◽  
pp. 138 ◽  
Author(s):  
Tanmoy Gangopadhyay ◽  
Ananya Mandal ◽  
Uma Shanker Keshri
Keyword(s):  
Seizure Threshold ◽  
Albino Rats ◽  
P Value ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Albino Rat ◽  
Co Morbidity ◽  
Significant Difference ◽  
Electroconvulsive Seizure

Background: Individuals with epilepsy have a higher incidence of psychiatric disorders than person without epilepsy. Epidemiological studies have shown that the co-morbidity of epilepsy and depression to be high as 50%. The conventional anti-depressants are believed to lower the seizure threshold making it difficult to treat the co-morbid depression, but animal studies have shown SSRIs, a common anti-depressant, to have anti-convulsant properties. So, we propose to study the anticonvulsant effects of fluoxetine, a SSRI, in albino rats against maximal electroshock seizure and to compare against a standard antiepileptic drug phenytoin.Methods: The anticonvulsant effect of fluoxetine was observed in model of maximal electroconvulsive seizure threshold in albino rats. The animals were divided into 3 groups having 6 animals each, receiving distilled water, fluoxetine and phenytoin respectively. The drugs were given orally, and the effect was observed on day 7, 14 and 21. Tonic hind-limb extension was taken as the parameter of electroshock seizure. The effects were compared against a standard anti-seizure drug phenytoin.Results: Fluoxetine showed significant elevation of the seizure threshold following 14 days of administration (P value 0.031). The effect was comparable to phenytoin with no significant difference after 7, 14 and 21 days of treatment (P-value 0.485, 0.699 and 0.818 respectively) though phenytoin showed significant anti-seizure effect since day 7 of treatment.Conclusions: Fluoxetine showed significant anti-seizure activity against electroconvulsive seizure in albino rats.

Discovery of novel substituted N-(6-Chloro-3-cyano-4-phenyl-4H-chromen-2-yl)-2-(4-chloro-phenoxy)-acetamide for biphasic anticancer and anticonvulsant activities

2019 ◽  
Vol 15 ◽  
Author(s):  
Divya Chauhan ◽  
Syed Riaz Hashim ◽  
Priyanka Rani ◽  
Sushil Kumar ◽  
Navratan Shrimal ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Computational Study ◽  
Colon Adenocarcinoma ◽  
Human Colon ◽  
Pharmacokinetic Profile ◽  
Seizure Threshold ◽  
Anticonvulsant Effect ◽  
Maximal Electroshock ◽  
Maximal Electroshock Seizure ◽  
Ht 29

Background : Privileged 4H-chromenes possess the potent anticancer and anticonvulsant actives. By inspiring potency of 4H-chromenes and demands of present era of scaffold, discovery of effective molecule was carried out for the treatment of cancer and conversant. Objective : Designed and synthesized a novel series of 4H-chromene derivatives from one port synthesis for the treatment of cancer and conversant. Method : Substitution of side amide chain was formed in multiple steps on amine group of chromene. Later, anticancer activity of synthesized compounds was investigated against human colon adenocarcinoma cell line (HT-29) using sulforhodamine B (SRB) assay. Moreover, anticonvulsant activity was also screened out by using maximal electroshock seizure (MES) model and subcutaneous Metrazol Seizure Threshold Test (scMET) in albino Wistar rats. Neurotoxicity was evaluated using by rotarod test. Before the synthesis, docking studies were performed using various molecular targets. Subsequently, the computational study of the titled compounds was performed to predict the pharmacokinetic profile. Result: Among the fifteen tested compounds, A4 and A9 were found to be active against HT-29 cells (growth inhibitory dose 50% (GI50) <11µM). Moreover, compounds A4 showed the protection at 300mg/kg in scMET (h) for albino Wistar rats and compounds A9, A11, A15 exhibited the anticonvulsant effect at the doses 100, 300 and 300 mg/kg, respectively in MES screen(h). Conclusion : Due to these encouraging results, we concluded that both A4 and A9 may be effective against colon cancer. While compound A9 may be used as a considerable effective molecule for the treatment of epilepsy.

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