Sundararajan Raja

Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives

Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5c, 5g, 5j and 5n were found active in MES model, while 5o showed significant antiepileptic activity in scPTZ model. Further all these five compounds were administered orally to rats, 5c, 5g and 5n showed better activity than Phenytoin in oral route. Among these compounds 5c revealed protection in MES at a dose of 30 mg/kg and 100 mg/kg 0.5 h and 4 h after i.p. administration respectively. This molecule provided also protection in the scPTZ at a dose of 300 mg/kg in both time intervals.

Novel 1-(4-substituted benzylidene)-4-(1-(substituted methyl)-2,3-dioxoindolin-5-yl)semicarbazide derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) and MDR-TB strain

A series of eighteen new 1-(4-substituted benzylidene)-4-(1-(substituted methyl)-2,3-dioxoindolin-5-yl)semicarbazide derivatives were designed, synthesized and characterized by spectral and elemental analyses. The derivatives were screened in vitro for antimicrobial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) and MDR-TB strains. The activity was expressed as the minimum inhibitory concentration in μg/mL. Among the tested compounds 7j, 7m, 7o and 7q possesses equipotent activity as standard drug Isoniazid against MTB while 7m and 7q exhibited higher activity against MDR-TB strain when compared with both the reference drugs isoniazid and rifampicin. Basic structure activity relationships are presented.

Anticonvulsant Activity of Novel 1‐(Substituted Benzylidene)‐4‐(1‐(Morpholino/Piperidino Methyl)‐2,3‐Dioxoindolin‐5‐yl) Semicarbazide Derivatives in Mice and Rats Acute Seizure Models

A series of novel 1‐(substituted benzylidene)‐4‐(1‐(morpholino/piperidino methyl)‐2,3‐dioxoindolin‐5‐yl) semicarbazides 6a–6t was designed and synthesized on the basis of semicarbazide‐based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The compounds were subjected to in vivo antiepileptic evaluation using maximal electroshock test and subcutaneous pentylenetetrazole seizure test methods. The neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 6c, 6d, 6g, 6h, and 6m were found active in maximal electroshock test model, while 6g, 6i, 6m, and 6o showed significant antiepileptic activity in subcutaneous pentylenetetrazole seizure test model. Further, the compounds 6c, 6d, 6g, 6h, 6i, and 6m were administered orally to rats, of which 6c and 6g showed better activity than phenytoin. Among the synthesized compounds, 6g revealed excellent protection in both models with lower neurotoxicity.