The anticonvulsant activity of diphenylhydantoin (DPH or phenytoin) is consistent with its actions on the neuronal voltage-dependent sodium channel. To further elucidate the binding requirements for this site, we synthesized several hydantoin analogs and evaluated these in in vitro sodium channel-binding and/or in vivo whole animal anticonvulsant assays. 5-Pentyl-5-phenylhydantoin (8), the most potent binder to the sodium channel in this study, had the same affinity as DPH (IC50 = 40 microM), revealing that one phenyl ring is sufficient for good interactions. Since our previous studies with monophenyl-substituted bicyclic 2,4-oxazolidinediones suggested that N3-alkylation and the conformational constraint of a 5-alkyl substituent over one face of the oxazolidinedione ring improved activity, we synthesized two examples of analogous bicyclic hydantoins. However, the bicyclic hydantoins were much less potent binders to the neuronal voltage-dependent sodium channel than their monocyclic counterparts. The binding activity for the more potent bicyclic hydantoin, 1,8-diaza-9,10-dioxo-7-phenylbicyclo[5.2.1]decane (4) (IC50 = 427 microM), was comparable to that of the ring-opened, N3-methylated monocyclic hydantoin model, 5-butyl-3-methyl-5-phenylhydantoin (9) (IC50 = 285 microM), and these were 8-11 times less potent than the monocyclic model 8, which contains a free imide NH. Furthermore, 5-butyl-5-phenylhydantoin (7; IC50 = 103 microM) was less potent than 8, suggesting that increased log P may enhance binding. Thus, unlike 2,4-oxazolidinediones, N3-alkylation of hydantoins dramatically decreases sodium channel-binding activity. Bicyclic hydantoin 4 was nevertheless a good anti-MES anticonvulsant in mice (ED50 = 86 mg/kg), although this activity likely results from mechanisms other than interactions at the neuronal voltage-dependent sodium channel. Compound 4 was also relatively neurotoxic (TD50 = 124 mg/kg). These results suggest that the binding of hydantoins to the sodium channel may be enhanced by (a) a free imide NH group and (b) an increased log P. Furthermore, 2,4-oxazolidinediones and hydantoins must either orient differently in the same binding site or interact with different sites on the neuronal voltage-dependent sodium channel.

The biosynthesis of silver nanoparticles (AgNPs) was achieved for the first time using methanol leaf extract of C. didymobotyra and their in vitro antioxidant and antibacterial activities were also evaluated. Methanol leaf extracts of C. didymobotyra after mixing with AgNO3 solution showed the change in color from light brown to dark yellowish brown within 1 hour. UV-visible spectroscopy study showed the surface plasmon resonance at around 420 nm clearly indicating the biosynthesis of AgNPs. Transmission Electron Microscopy (TEM) analysis proved the presence of biosynthesized AgNPs in spherical shape with huge disparity in sizes. The average size of biosynthesized nanoparticle was about 18 nm. The occurrence of face centered cubic shapes of nanoparticles was established by X-ray diffraction (XRD) patterns. Further, Fourier transform infrared spectroscopy (FTIR) study showed the possible capping of AgNPs because of the active biomolecules present in the methanol leaf extract of C. didymobotyra. The antioxidant activities of biosynthesized AgNPs were evaluated by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging assay and found that AgNPs demonstrated a strong antioxidant properties compared to methanol leaf extract. Nevertheless, the biosynthesized AgNPs exhibited a strong antibacterial activity against all the tested human pathogenic bacterial strains compared to crude methanol leaf extract of C. didymobotyra. Thus, it is concluded that these biosynthesized AgNPs are cost effective, eco-friendly in nature and could be applied for developing new antibacterial drugs and other biomedical applications in near future.

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Blood glucose and total lipid levels of normal and alloxantreated diabetic rabbits were determined after oral administration of various doses of the Cuminum nigrum L. seeds and their extracts in water and methanol. From the data obtained, it is concluded that the oral administration of 1,2, 3 and 4 g/kg of C. nigrum seeds produces a significant hypoglycaemic effect in normal as well as in diabetic rabbits. The water and methanol extracts also decreased the blood glucose level in normal and alloxan-diabetic rabbits. However, the total blood lipids were not influenced by this substance in either normal or diabetic rabbits. The acute toxicity studies carried out on rabbits could not reveal any adverse or side effects of this folk medicine at the dosages tested. It is suggested that the C. nigrum seeds contain one or more hypoglycaemic principles which can significantly reduce the blood glucose but not total lipids level in normal rabbits and in those with alloxan-induced diabetes.

Summary:Taurolidine has been shown to have remarkable cytotoxic activity against selected human tumor cells at concentrations that spare normal cells. In this study we have extended this observation and assessed the ability of Taurolidine