Design and synthesis of (5-amino-1, 2, 4-triazin-6-yl)(2-(benzo[d] isoxazol-3-yl) pyrrolidin-1-yl)methanone derivatives as sodium channel blocker and anticonvulsant agents.

A series of novel (5-amino-3-substituted-1, 2, 4-triazin-6-yl) (2-(6-halo-substituted benzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5a-5r was synthesized. Their anticonvulsant activities were evaluated by the maximal electroshock (MES) test and neurotoxicity was evaluated by the rotorod test. The MES test showed that (5-amino-3-phenyl-1, 2, 4-triazin-6-yl)(2-(6-fluorobenzo[d]isoxazol-3-yl) pyrrolidin-1-yl) methanone 5c was found to be the most potent compound with ED50 value of 6.20 mg/kg (oral/rat) and a protective index (PI = ED50/TD50) value of >48.38, which was much higher than the PI of the reference drug phenytoin. To explain the possible mechanism of action of selected derivatives 5 b, 5 c, 5 i and 5 o, their influence on sodium channel was evaluated in vitro.

Design, synthesis and evaluation of N-(substituted benzothiazol-2-yl)amides as anticonvulsant and neuroprotective.

A series of N-(substituted benzothiazol-2-yl)amide derivatives 2a-h and 4a-h were synthesized by the EDC coupling reactions of substituted-benzothiazol-2-amine with 4-oxo-4-phenylbutanoic acid/2-benzoyl benzoic acid and evaluated for their anticonvulsant and neuroprotective effect. N-(6-methoxybenzothiazol-2-yl)-4-oxo-4-phenylbutanamide (2f) emerged as the most effective anticonvulsant with median doses of 40.96 mg/kg (MES ED(50)), 85.16 mg/kg (scPTZ ED(50)) and 347.6 mg/kg (TD(50)). Furthermore, compound 2f displayed promising neuroprotective effect by lowering the levels of MDA and LDH; therefore, it represents a potential lead in search for safer and effective anticonvulsants having neuroprotective effects.

Synthesis and antimicrobial screening of N-[2-(2/4-substituted phenyl)-1-(5/6 substituted 1H- benzimidazol-2-yl)vinyl]benzamides.

A series of (benzamidostyryl)benzimidazole derivatives were synthesized by hydrolyzing 2-phenyl-4-(substituted)benzylidene-5-oxazolones, the azlactone precursors in an acidic medium and treating the product with substituted o-phenylenediamine (OPDA) in situ. The structures of the synthesized compounds were confirmed by spectral and elemental analyses. All synthesized compounds were screened for their in vito antimicrobial activities against some identifiable strains. Thereby, it was found that only nitro substituted benzimidazoles exhibited good to moderate antibacterial activity, while other derivatives were devoid of any antimicrobial effect.

Design, synthesis and screening of quinoline-incorporated thiadiazole as a potential anticonvulsant.

A series of quinoline-incorporated substituted thiadiazole were designed and synthesized using appropriate synthetic route keeping in view the structural requirement of pharmacophore and evaluated for anticonvulsant and CNS activities. After intraperitoneal injection to mice, some synthesized derivatives were examined in the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPTZ)-induced seizure and neurotoxicity screens. Those found potent were also evaluated for behavioural impairment and depression activity. Among the compounds tested, 6d and 6e showed protection from seizures in both the animal models at dose level of 30 mg/kg while 7f showed protection against both models at 100 mg/kg dose level. These compounds exhibited lesser CNS depression and neurotoxicity compared with clinically effective drug.

Synthesis and in vitro antimicrobial activity of novel N-(6-chlorobenzo[d]thiazol-2-yl) hydrazine carboxamide derivatives of benzothiazole class.

In this study, a series of novel 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (6a-g) and 1,3,4-oxadiazole (7a-g, 8) were synthesized from N-(6-chlorobenzo[d]thiazol-2-yl) hydrazine carboxamide derivatives of benzothiazole class. Antimicrobial properties of the title compound derivatives were investigated against one Gram (+) bacteria (Staphylococcus aureus), three Gram (-) bacteria (Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae) and five fungi (Candida albicans, Aspergillus niger, Aspergillus flavus, Monascus purpureus and Penicillium citrinum) using serial plate dilution method. The investigation of antibacterial and antifungal screening data revealed that all the tested compounds showed moderate to good inhibition at 12.5-100 µg/mL in DMSO. It has been observed that triazolo-thiadiazole derivatives are found to be more active than 1,3,4-oxadiazole derivatives against all pathogenic bacterial and fungal strains.

Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: synthesis and pharmacological evaluation.

A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4-(substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1-30) were designed and synthesized keeping in view the structural requirements as suggested in the pharmacophore model for antihypertensive activity. All the synthesized compounds were tested for antihypertensive activity by non-invasive blood pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested compounds displayed considerable decrease in the blood pressure as compared to control. Thirteen compounds showed significant antihypertensive activity comparable to the standard drug nifedipine.

Phytochemical investigation of the seeds of Althea officinalis L.

Phytochemical investigation of the seeds of Althea officinalis L. (Malvaceae) led to the isolation of three new phytoconstituents, identified as n-hexacos-2-enyl-1,5-olide (altheahexacosanyl lactone), 2beta-hydroxycalamene (altheacalamene) and 5,6-dihydroxycoumarin-5-dodecanoate-6beta-D-glucopyranoside (altheacoumarin glucoside), along with the known phytoconstituents lauric acid, beta-sitosterol and lanosterol. The structures of these compounds were established on the basis of spectral analysis and chemical reactions.

Synthesis and pharmacological evaluation of condensed heterocyclic 6-substituted 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives of isoniazid.

The significance of this study was to prepare various isoniazid derivatives by introducing the isoniazid core into several molecules to explore the possibilities of some altered biological activities. Series of 6-substituted-1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole (3a-g) and 1,3,4-oxadiazole (4a-g and 5) derivatives of isoniazid were synthesized in satisfactory yield and pharmacologically evaluated for their anti-inflammatory, analgesic, ulcerogenic, and lipid peroxidation activities by known experimental models.

Stability-indicating high-performance thin-layer chromatographic method for quantitative determination of omeprazole in capsule dosage form.

A novel HPTLC method has been developed and validated for quantitative determination of omeprazole (OPZ) in capsule dosage form. The method was validated according to the International Conference on Harmonization guidelines for accuracy, precision, linearity, specificity, and robustness. HPTLC aluminum sheets precoated with silica gel 60F24 were used as the stationary phase and chloroform-methanol (9 + 1) as the mobile phase. The mobile phase was found to give compact bands for OPZ (Rf value of 0.39 +/- 0.12) in densitometric analysis in the absorbance mode at 302 nm. The linear regression analysis data for the calibration plots showed good linearity (r2 = 0.997) with respect to peak area in the concentration range 50-3000 ng/band. The mean values of the slope and intercept were 9.896 +/- 0.0753 and 1870.761 +/- 16.866, respectively. The method was also applied for stability testing of OPZ in different stress conditions and found to be accurate, linear, precise, robust, specific, and stability indicating. The method proposed can be used for QC and stability testing of different dosage forms such as tablets and capsules, as well as for bulk drug analysis of OPZ.

Synthesis, anticonvulsant and toxicity screening of newer pyrimidine semicarbazone derivatives.

A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a-t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.

Sulfonamide derivatives of thiazolidin-4-ones with anticonvulsant activity against two seizure models: synthesis and pharmacological evaluation.

A series of 4-thiazolidinones bearing a sulfonamide group (4a-w) were prepared by cyclizing various 5-bromo-2-methoxy-N'-[(1E)-arylmethylene/arylethylidene]benzenesulfonohydrazides. All the compounds were characterized by IR, (1)H NMR, and elemental analysis. The compounds were tested for their anticonvulsant activity utilizing MES and scPTZ animal models. The majority of the compounds exhibited significant activity against both animal models; however, compounds 4c, 4m, and 4o displayed promising activity and could be considered as leads for further investigations.

Synthesis and preliminary screening of benzothiazol-2-yl thiadiazole derivatives for anticonvulsant activity.

Various N-(5-chloro-6-substituted-benzothiazol-2-yl)-N'-(substituted phenyl)-[1,3,4]thiadiazole-2,5-diamines (5a-t) were designed and synthesized starting from substituted acetophenones. Structures of all the compounds were confirmed on the basis of spectral and elemental analyses. All the newly synthesized compounds were screened for their anticonvulsant activity and were compared with the standard drug phenytoin sodium. Interestingly, all the compounds showed protections against seizures in the range 50-100% indicative of the promising nature of the compounds against seizure spread. Compounds 5b and 5c showed complete protection against MES induced seizures.

Synthesis of 8-substituted-4-(2/4-substituted phenyl)-2H-[1,3,5]triazino[2,1-b][1,3]benzothiazole-2-thiones and their anticonvulsant, anti-nociceptive, and toxicity evaluation in mice.

A number of new 8-substituted-4-(2/4-substituted phenyl)-2H-[1,3,5]triazino[2,1-b][1,3]benzothiazole-2-thiones (4a-t) were synthesized and evaluated for their anticonvulsant, anti-nociceptive, hepatotoxic, and neurotoxic properties. The titled compounds (4a-t) were obtained by cyclization of N-{[6-substituted-1,3-benzothiazol-2-yl)amino]carbonothioyl}-2/4-substituted benzamides (3a-t) by refluxing in n-butanol. All the newly synthesized compounds were screened for their anticonvulsant activity in a mouse seizure model and were compared with the standard drug phenytoin. Compounds 4a, 4c, 4f, and 4l showed complete protection after time periods of 0.5 h and 4 h. Some of the selected compounds were evaluated for their neurotoxic and hepatotoxic effects, and none of these showed any sign of neurotoxicity or hepatotoxicity. Compounds 4a-t were also evaluated for their anti-nociceptive activity by a thermal stimulus technique using diclofenac as standard. Compounds 4o, 4q, and 4t displayed highly potent analgesic activity with p < 0.01.

Synthesis of hydrazones derivatives of quinoxalinone--prospective antimicrobial and antiinflammatory agents.

A series of quinoxalinone derivatives was synthesized by the condensation of 1,2-diaminobenzene with alpha-ketoglutaric acid to yield 3-(3-oxo-3,4-dihydroquinoxalin-2-yl) propionic acid (2) and then treated with hydrazine hydrate to yield its hydrazones (3). This was further reacted with substituted aromatic aldehydes to produce final compounds (4a-r). These hydrazones derivatives were characterized by FT-IR and 1H-NMR data. All the synthesized compounds were evaluated for their antimicrobial and antiinflammatory activity.

Synthesis of some new coumarin incorporated thiazolyl semicarbazones as anticonvulsants.

Several heteroaryl semicarbazones were prepared by the reaction of heteroaryl hydrazine carboxamide with aryl aldehydes or ketones. The structures of the synthesized compounds were confirmed by spectral data and elemental analyses. Compounds were tested for anticonvulsant activity utilizing pentylenetetrazole-induced seizure (PTZ) and maximal electroshock seizure (MES) tests at 30, 100 and 300 mg/kg dose levels. Neurotoxicity of the compounds was also assessed at the same dose levels. Three compounds of the series, 6d, 6i and 6n, exhibited significant anticonvulsant activity at 30 mg/kg dose level comparable to the standard drug, phenytoin.

Synthesis of 1,2,4-triazine derivatives as potential anti-anxiety and anti-inflammatory agents.

A series of 1,2,4-triazine derivatives Va (1-24) and Vb (1-24) were synthesized and evaluated for their anti-anxiety and anti-inflammatory activities. The structures of the synthesized compounds were confirmed on the basis of their spectral data. Many of the triazine compounds were found to possess good activity. Especially, compounds bearing the sulfur atom showed better activity than those bearing the oxygen atom.

Anticonvulsant and neurotoxicity evaluation of new bromophthalimidobutyryl amide derivatives.

A series of 4-(5-bromo-1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-butyryl N-(substituted phenyl) amides (3a-I) were synthesized and evaluated for their anticonvulsant activity in MES test according to the protocols of Antiepileptic Drug Development (ADD) programme of National Institutes of Health (NIH, Bethesda, USA).The most active compounds of the series were 3a, 3c, 3d, 3f, 3g, 3i and 3k at the dose of 30 mg/kg (i.p.) 0.5 h and 4 h after administration. In neurotoxic screen (NT), 3d, 3i and 3k were less toxic when compared with the other compounds.

Synthesis of triazolothiazolidinone derivatives of coumarin with antimicrobial activity.

A series of 2-(substituted phenyl)-3-[3-(2-oxo-2H-chromen-3-yl)-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl]-1,3-thiazolidin-4-ones, 8a-n, were synthesized and evaluated for their antimicrobial activity. The structures of the compounds were confirmed on the basis of their elemental analysis and spectral data. Compounds 8k, 81 and 8m showed significant inhibition against S. aureus, compound 8m showed significant inhibition against E. coli and compounds 8b, 8e, 8i, 8j, 8k, 81 and 8m showed significant inhibition against C. albicans.

Synthesis of novel 3-(4-acetyl-5H/methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromen-2-ones as potential anticonvulsant agents.

A series of 3-(4-acetyl-5H/methyl-5-substituted phenyl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2H-chromene-2-ones (6a-j) were synthesized and evaluated for anticonvulsant activity and neurotoxicity. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. A majority of the compounds was active in MES tests. Compound (6e) was found to be potent and had activity at lower dose of 30 mg/kg in MES-test. All the compounds were less toxic as compared with the standard drug phenytoin.