Anticonvulsant Activity and Toxicity Evaluation of Cu^II and Zn^II Metal Complexes Derived from Triazole-Quinoline Ligands

Abstract

Epilepsy is an ever-present serious disease related to the neurological disorders. It is generally characterized by recurrent seizures that result from phasic changes in the firing properties of groups of neurons. The induction of a group of neurons into a pattern of burst-firing results in synchronized disruptive seizure discharge. The detailed studies reveals that, the excitatory and inhibitory neurotransmission as well as voltage-gated channels (that can be modulated selectively by natural or synthetic toxins) are the two major factors, that are found to be the crucial for seizure like activity.1,2) The antiepileptic drugs, which are in efficacious clinical practice, act by inducing prolonged inactivation of the Na ϩ channel, by blocking Ca 2ϩ channel currents or by enhancing inhibitory g-aminobutyrate (GABA)-ergic neurotransmission. Some of the other anticonvulsant agents act via a number of different mechanisms, which may include antagonism of glutamateergic neurotransmission.3) However it is seen that, the majorities of antiepileptic drugs do not provide satisfactory seizure control in all patients and typically cause notable adverse side effects. 4,5) It is hence becomes a crucial and challenging task in the field of medicinal chemistry to find more efficient and safer antiepileptic agents.In this regard, there are few attempts made, the organic moieties having anticonvulsant property were interacted with suitable metal ions and hence formed complexes are investigated for the anticonvulsant activity. Interestingly, a considerable enhancement of activity upon complexation has been observed, 6,7) which is certainly related to the increased lipophilicity upon complexation (which increases their permeability to the blood-brain barrier) and inertness of certain metal ligand linkages towards enzymatic degradation. 8,9) Quinoline derivatives have been known to possess a variety of biological activities such as antitumor, 10) antimalarial, 11) antidepressant, 12) antiulcer 13) and cardiac stimulant. 14)Along with these, there are reports suggesting that the quinolines have exhibited a very good anticonvulsant activity in the maximum electroshock method test. 15) In this regard, so many attempts are made by incorporating various hetero cyclic groups to the quinoline core, in order to obtain compounds with better anticonvulsant activity.16,17) Substitution of triazole or triazolone ring to the quinoline core has been found to increase receptor binding capacity and metabolic stability, which in turn enhances the anticonvulsant activity of the compound. 18,19) In the present research work, we have selected 2-hydroxy, 3-formyl quinoline as a precursor. The presence of oxygen functional groups in the quinoline core is expected to facilitate the elliptical activity 20) as well as complexation. Amino triazoles are incorporated to the precursor by means of Schiff base formation in the presence of Cu II and Zn II ions (these two are selected by considering the higher bioaccessiblity, as compared to the other transition met...

Metal(II) Ion Complexes with 5‐(Pyrazin‐2‐yl)‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thione; Synthesis, Structural Characterization, Acid‐base, and Complexing Properties in Solution

“…The triazole rings are known to be pharmacologically important scaffolds in a variety of drug categories . Their derivatives and metal complexes have been reported as antimicrobial,, antiviral, antitumor, anticonvulsant, antidepressant, analgestic, and anti‐inflammatory agents…”