OBJECTIVETo study the effect of halo substitution on disubstituted aryl semicarbazones on the anticonvulsant potential and model the activity based on quantum mechanics.

METHODSA series of twenty-six compounds of N(4)-(4-bromo-3-methylphenyl) semicarbazones were synthesized and evaluated for the anticonvulsant activity in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure threshold tests. Some potential compounds were also tested in the subcutaneous strychnine (scSTY) and subcutaneous picrotoxin (scPIC) seizure threshold tests. The synthesized compounds were tested for behavioral impairment and CNS (central nervous system) depression in mice. Quantum mechanical modelling was carried out on these compounds to gain understanding on the structural features essential for activity.

RESULTSSome compounds possessed broad spectrum anticonvulsant activity as indicated by their effect in pentylenetetrazole, strychnine, picrotoxin and maximal electroshock seizures models in resemblance to other aryl semicarbazone derivatives reported earlier. The higher the difference in HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) energy levels was, the greater was the activity profile.

CONCLUSIONThe pharmacophoric requirements for compounds to exhibit anticonvulsant activity that includes one aryl unit in proximity to a hydrogen donor-acceptor domain and an electron donor have been justified with the molecular orbital surface analysis of the synthesized compounds.

Animals ; Anticonvulsants ; chemical synthesis ; chemistry ; pharmacology ; Male ; Mice ; Models, Molecular ; Molecular Structure ; Quantum Theory ; Rats ; Rats, Sprague-Dawley ; Semicarbazones ; chemical synthesis ; chemistry ; pharmacology ; Thermodynamics

OBJECTIVEA series of 4-aryl substituted semicarbazones of levulinic acid (4-oxo pentanoic acid) was designed and synthesized to meet the structural requirements essential for anticonvulsant activity.

METHODSAll the compounds were evaluated for anticonvulsant activity. Anticonvulsant activity was determined after intraperitoneal (i.p.) administration to mice by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test.

RESULTSA majority of the compounds exhibited significant anticonvulsant activity after intraperitoneal administration. In the present study 4-(4'-fluoro phenyl) levulinic acid semicarbazone emerged as the most active molecule, showing broad spectrum of activity with low neurotoxicity. Unsubstituted levulinic acid semicarbazone was found to be inactive in all the screens.

CONCLUSIONThe results obtained validate the hypothesis that presence of an aryl group near the semicarbazone moiety is essential for anticonvulsant activity. The results also indicate that the hydrophilic-hydrophobic site can accommodate hydrophilic groups.

Animals ; Anticonvulsants ; administration & dosage ; adverse effects ; analysis ; chemistry ; Drug Evaluation, Preclinical ; Injections, Intraperitoneal ; Levulinic Acids ; administration & dosage ; adverse effects ; analysis ; chemistry ; Mice ; Seizures ; drug therapy ; Semicarbazones ; administration & dosage ; adverse effects ; analysis ; chemistry ; Treatment Outcome

OBJECTIVETo determine the hepatoprotective effect of acetone semicarbazone (ASC) in vivo in normal and Ehrlich ascites carcinoma (EAC) bearing male Swiss albino mice.

METHODSDrug-induced changes in biochemical and behavioral parameters at dose of 2.0 mg/kg body weight for 14 d and nullifying the toxicity induced by EAC cells were studied. The histopathology studies of the protective effects of ASC on vital organs were also assessed.

RESULTSThe administration of ASC made insignificant changes in body weight and behavioral (salivation, diarrhea, muscular numbness) changes during treatment period due to minor toxicity were minimized after the treatment in normal mice. The biochemical parameters, including serum glutamate pyruvate transaminase, glutamate oxaloactate transaminase, alkaline phosphatase, serum glucose, cholesterol, urea, triglyceride and billirubin changed modestly in normal mice receiving ASC. Though the treatment continued, these values gradually decreased to normal level after the treatment. In EAC bearing mice, the toxic effects due to EAC cells in all cases were nullified by treatment with the ASC. Significant abnormalities were not detected in histology of the various organs of the normal mice treated with ASC.

CONCLUSIONSASC can, therefore, be considered safe in formulating novel anticancer drug, as it exhibits strong protective effect against EAC cell bearing mice.

Acetone ; analogs & derivatives ; pharmacology ; therapeutic use ; Animals ; Antineoplastic Agents ; pharmacology ; therapeutic use ; Carcinogenesis ; drug effects ; Carcinoma, Ehrlich Tumor ; drug therapy ; Liver ; drug effects ; Male ; Mice ; Semicarbazones ; pharmacology ; therapeutic use

A case of Toxic Epidermal Necrolysis affecting 24 years old, male Korean, who has been suffering from Pulmonary Tuberculosis, is presented. The skin lesions of the case have been developed about two months after administration of Thioacetazone, 150 mg. per day. The cause of this case may be due to Thioacetazone, one of the antituberculous drugs. Diagnosis of Toxic Epidermal Necrolysis was estsblished by clinical characteristics, histopathological and laboratory studies, and review of literatures were made also.
Diagnosis ; Humans ; Male ; Skin ; Stevens-Johnson Syndrome* ; Thioacetazone ; Tuberculosis, Pulmonary ; Young Adult

In laboratory some complexes of platin II, copper II, nikel II with diacetyl monoxin thiosemicarbazon were synthetized. The structure of these complexes and components were determind with UV, UR spectroscopy. The antimiorobial activities were examined on Gram (-) and Gram (+) bacteria, fungi and yeast. Results showed strong antibacterial activities of these synthetized complexes.
Thiosemicarbazones ; Biology ; Bacteria

Induced pluripotent stem cells (iPSCs) can be propagated indefinitely, while maintaining the capacity to differentiate into all cell types in the body except for the extra-embryonic tissues. This iPSC technology not only represents a new way to use individual-specific stem cells for regenerative medicine but also constitutes a novel method to obtain large numbers of disease-specific cells for biomedical research. However, the low efficiency of reprogramming and genomic integration of oncogenes and viral vectors limit the potential application of iPSCs. Chemical-induced reprogramming offers a novel approach to generating iPSCs. In this study, a new combination of small-molecule compounds (SMs) (sodium butyrate, A-83-01, CHIR99021, Y-27632) under conditions of transient folate deprivation was used to generate iPSC. It was found that transient folate deprivation combined with SMs was sufficient to permit reprogramming from mouse embryonic fibroblasts (MEFs) in the presence of transcription factors, Oct4 and Klf4, within 25 days, replacing Sox2 and c-Myc, and accelerated the generation of mouse iPSCs. The resulting cell lines resembled mouse embryonic stem (ES) cells with respect to proliferation rate, morphology, pluripotency-associated markers and gene expressions. Deprivation of folic acid, combined with treating MEFs with SMs, can improve the inducing efficiency of iPSCs and reduce their carcinogenicity and the use of exogenous reprogramming factors.
Amides ; pharmacology ; Animals ; Butyric Acid ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Extraembryonic Membranes ; cytology ; drug effects ; Folic Acid ; pharmacology ; Induced Pluripotent Stem Cells ; cytology ; drug effects ; Kruppel-Like Transcription Factors ; metabolism ; Mice ; Octamer Transcription Factor-3 ; metabolism ; Proto-Oncogene Proteins c-myc ; metabolism ; Pyrazoles ; pharmacology ; Pyridines ; pharmacology ; Pyrimidines ; pharmacology ; SOXB1 Transcription Factors ; metabolism ; Thiocarbamates ; pharmacology ; Thiosemicarbazones