ORIGINAL PAPER Exploration on structure and anticonvulsant activity of transition metal complexes derived from an ‘‘end-off’’ compartmental bis- quinoxaline derivative with phthalazinyl-diazine as endogenous bridge Srinivasa Budagumpi • Naveen V. Kulkarni • M. P. Sathisha • Sandeep P. Netalkar • Vidyanand K. Revankar • D. K. Suresh Received: 10 February 2010 / Accepted: 14 February 2011 / Published online: 18 March 2011 Ó Springer-Verlag 2011 Abstract An oligoquinoxaline derivative with phthal- azine core has been prepared by condensation of 1,4- dihydrazinophthalazine with 2,3-dichloroquinoxaline in dry ethanol followed by acid hydrolysis. Classical endog- enous bridging of phthalazine core with its diazine fragment was established in the transition metal(II) com- plexes derived from the ligand system by using various physicochemical and spectral techniques. The organic host acts as a hexadentate chelate with N 4 O 2 donating sites for coordination towards later first-row transition metal ions. Complexes are in good agreement with the octahedral geometry and found to be 1:1 electrolytes. All synthesized compounds were screened for anticonvulsant activity in Wistar rats by using maximal electroshock method. The ligand, and Co(II) and Ni(II) complexes show appreciable suppression towards electroshock-induced seizures. Keywords Quinoxaline Á Phthalazine Á Anticonvulsant Á Octahedral Á Maximal electroshock Á Seizures Introduction It is found in literature that 1,4-disubstituted phthalazine, quinoxaline, quinoline, and benzodiazepine derivatives are potent anticonvulsants, as they can strongly resist the unwanted evoked currents in the cerebella neurons growth in brain [1–5]. The central nervous system (CNS) is governed by inhibitory amino acids on the one hand, viz. gamma- aminobutyric acid (GABA), and excitatory amino acids on the other hand (glutamate). The ligand-gated ion channels (LGICs) encompass kainate, (S)-2-amino-3-(3-hydroxy- 5-methylisoxazol-4-yl)propionic acid (AMPA), and N-methyl-D-aspartic acid (NMDA) receptors. NMDA receptors are permeable to sodium, calcium, and potassium ions, following the direction of their natural gradient. The most characteristic feature of the NMDA receptor is its voltage-dependent regulation by magnesium, which means the channel pore can only be opened if partial depolarization has proceeded. It is evident from the reports that the men- tioned compounds, especially 1,4-disubstituted phthalazine and benzodiazepine derivatives with quinoxaline substitu- tions, do act as AMPA/kainate receptor antagonists, hence becoming drugs of choice for epilepsy. In particular, 3-substituted quinoline and quinoxaline derivatives are also known for epileptic activity [6], since their structures resemble reported anticonvulsants docu- mented in the literature. In this work, we attempt to introduce a hydrazide fragment attached to the phthalazine ring, which is also an anticonvulsant agent, at 3-position of the quinoxaline ring to enhance the activity of the com- pounds formed. The acyclic multinucleating ligands possessing two chelating arms and central donor bridging atom(s) are called ‘‘end-off’’ compartmental ligands. Diazine (–N=N–) bridge-containing end-off compartmental ligands are of S. Budagumpi Á M. P. Sathisha Á S. P. Netalkar Á V. K. Revankar (&) Department of Chemistry, Karnatak University, Pavate Nagar, Dharwad 580 003, Karnataka, India e-mail: vkrevankar@rediffmail.com S. Budagumpi Department of Chemical Engineering, Pusan National University, Pusan 609-735, Republic of Korea N. V. Kulkarni Department of Chemistry, Technion - Israel Institute of Technology, 32000 Haifa, Israel D. K. Suresh Department of Pharmacology, Luqman College of Pharmacy, Gulbarga 585 102, Karnataka, India 123 Monatsh Chem (2011) 142:487–494 DOI 10.1007/s00706-011-0462-1