Anxiolytic-like effect of <i style="mso-bidi-font-style:normal">N</i>-n-butyl-3-methoxyquinoxaline-2-carboxamide (<b>6o</b>) in experimental mouse models of anxiety

510-514The present research was designed to explore the anxiolytic-like activity of a novel 5-HT3 receptor antagonist (6o) in experimental mouse models of anxiety. The anxiolytic activity of '6o' at (1 and 2 mg/kg, ip) was evaluated in mice by using a battery of behavioural tests of anxiety such as elevated plus maze (EPM), light/dark aversion test, hole board (HB) and open field test (OFT) with diazepam (2 mg/kg, ip) as a standard anxiolytic. None of the tested doses of '6o' affected the base line locomotion. Compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the percentage of both time spent and open arm entries in the EPM test. Compound '6o' in (1 mg/kg, ip) dose was only able to affect the percentage time spent in open arm significantly in the EPM test. In the light and dark test, compound '6o' (2 mg/kg, ip) and diazepam (2mg/kg, ip) significantly increased the total time spent in light compartment as well as number of transitions from one compartment to other and number of square crossed. Compound '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) also significantly increased number of head dips and number of squares crossed, whereas significantly decreased the head dipping latency in HB test as compared to vehicle control group. In addition, '6o' in both the doses and diazepam (2mg/kg, ip) significantly increased the ambulation scores (squares crossed) in OFT however, there was no significant effect of '6o' (1 and 2 mg/kg, ip) and diazepam (2 mg/kg, ip) on rearing scores. To conclude compound '6o' exhibited an anxiolytic-like effect in animal models of anxiety

Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (4-benzylpiperazin-1-yl)(3-methoxyquinoxalin-2-yl) methanone (6g) on lipopolysaccharide-induced anxiety models in mice

AbstractBackground:5-HTMethods:LPS, an endotoxin, present in the cell wall of Gram negative bacteria was injected 0.83 mg/kg, i.p. as a single dose to induce anxiety-like symptoms in mice. Compound 6g (1 and 2 mg/kg, p.o.) and standard fluoxetine (FLX) (20 mg/kg, p.o.) were injected to treatment groups for 7 days and evaluated in various behavioral paradigms such as elevated plus maze (EPM), light and dark (L/D) test, and open field test (OFT). Their effects on serotonin levels in mice brain were also examined.Results:The results showed that LPS induced anxiety-like symptoms in mice, as indicated by a significantly decreased percentage open arm entries and percentage time spent in open arms in EPM; decreased time spent in light area and number of transition between chambers in L/D test; decreased ambulation and rearing scores in OFT. Compound 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) reversed the LPS-induced behavioral changes and significantly affected all the behavioral parameters mentioned above. In addition 6g (1 and 2 mg/kg, p.o., 7 days) and FLX treatment (20 mg/kg, p.o., 7 days) increased the levels of serotonin in mice brain.Conclusions:Compound 6g produced anxiolytic-like effects in various anxiety paradigms in LPS-treated mice as well as restored the decreased serotonin levels in mice brain.</jats:sec

Anti-depressant like activity of <i>N</i>-n-butyl-3-methoxyquinoxaline-2-carboxamide (<b>6o</b>) a 5-HT₃receptor antagonist

435-443<span style="font-size:11.0pt;font-family: " times="" new="" roman";mso-fareast-font-family:"times="" roman";mso-bidi-font-family:="" mangal;mso-ansi-language:en-gb;mso-fareast-language:en-us;mso-bidi-language:="" hi"="" lang="EN-GB">The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, <b style="mso-bidi-font-weight: normal">6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound <b style="mso-bidi-font-weight: normal">6o exhibited anti-depressant like effect in rodent models of depression.</span

Design, synthesis and evaluation of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives as a new class of falcipain-2 inhibitors

AbstractThe cysteine protease, falcipain-2 is an important drug target in human malaria parasite Plasmodium falciparum. A new series of 2-(4-(substituted benzoyl)-1,4-diazepan-1-yl)-N-phenylacetamide derivatives 5(a–t) were designed as per pharmacophoric requirements of falcipain-2 inhibitors using ligand-based approach. The target compounds were synthesized from the key intermediate, 2-(1,4-Diazepan-1-yl)-N-phenylacetamide, by coupling it with appropriate carboxylic acids using carbodiimide chemistry. Structural features of target compounds were characterized by spectral data (1H NMR, and mass) and elemental analyses. The purity of the final compounds was confirmed by HPLC. The compounds were tested for their in vitro falcipain-2 inhibitor activity on recombinant falcipain-2 enzyme. Five compounds 5b, 5g, 5h, 5j, 5k showed good inhibitory activity (>60%), against falcipain-2 at 10μM concentration, and fifteen compounds showed weak to moderate inhibitor activity. Compound 5g, the most potent compound from this series showed 72% inhibition at 10μM concentrations