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Synephrine is a natural small-molecule alkaloid found in Aurantii fructus immaturus with versatile biological activities, but its derivatives have been rarely studied so far. Based on the multi-target drug design strategy, the phenolic hydroxyl and secondary amino group of synephrine were modified structurally by the molecular splicing method in this study and thus five intermediates and fifteen target molecules were designed and synthesized. These compounds were evaluated with certain human pathogenic bacteria and fungi, and found that the inhibitory activities of IM4 and IM5 against E.coli are comparable to those of eight fluoroquinolones; TM1n showed stronger inhibitory activity against drug-resistant C. trobicans and drug-resistant C. albicans than the positive control drug fluconazole. TM1d and TM1f against C. albicans ATCC90023, TM1o and TM1f against drug-resistant C. albicans, and TM1f against C. parapsilosis ATCC22019 are all comparable to fluconazole, all of which have the potential for in-depth research. In this study, synephrine derivatives with strong inhibitory activities against human pathogenic fungi were discovered for the first time, which provided a new idea for the further study of synephrine.
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Cancer a leading cause of human mortality worldwide is characterised by the unseemly growth of cellular mass and signalled through the enlargement of stress. Management of cancer treatment is still buried andhas been recently alerting the need to discover a drug molecule with lesser side effects. The objective of the present study is to explore the anticancer activity and docking studies of 1-(5-substituted phenyl) isoxazol-3-yl)-5-phenyl-1H-tetrazole derivatives. The compounds were evaluated for in-vitroanticancer activity under the drug discovery program of National Cancer Institute (NCI), USA. Only seven compounds were selected and screened for anticancer activity at a single high dose (10-5M) using NCI 60 cancer cell lines. Among all the selected compounds, 4band 4iexhibited significant anticancer activity against Leukemia cell lines. Molecular docking studies for the 5-phenyl-1-(5-substituted phenylisoxazol-3-yl)-1H-tetrazole analogues was done by Schrodinger software. Docking results stated that the compounds 4band 4ihas good dock score among the other derivatives which shows good binding efficiency towards receptor
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@#The aim of this study was to establish a high performance liquid chromatography-mass spectrometry method for the determination of 5-(4′-(bromomethyl)-［1, 1′-biphenyl］-2-yl)- 1H-tetrazole(BBT1)and 5-(4′-(dibromomethyl)-［1, 1′-biphenyl］-2-yl)-1H-tetrazole(BBT2), which are two genotoxic impurities in olmesartan medoxomil. Chromatographic separation was based on an Agilent Zorbax Eclipse Plus C18(250 mm × 4. 6 mm, 5 μm)column using water(containing 0. 1% formic acid)- acetonitrile as mobile phase in gradient elution mode. Mass spectrometry was operated in positive ion mode. Selective ion monitors were set at m/z 315 for BBT1 and at m/z 395 for BBT2. Good linear correlations were observed in the range of 0. 009 4- 0. 561 0 μg/mL(r=0. 998)with the quantification limit at 9. 35 ng/mL and the detection limit at 3. 12 ng/mL for BBT1, and in the range of 0. 018 2- 0. 547 5 μg/mL(r=0. 999)with the quantification limit at 18. 25 ng/mL and the detection limit at 6. 08 ng/mL for BBT2. Furthermore, the average recoveries of the three spiked concentration level were 96. 5%(n=9, RSD=4. 8%)and 98. 0%(n=9, RSD=5. 1%)for BBT1 and BBT2, respectively. The proposed method is simple, specific and accurate, and quite suitable for the determination of BBT1 and BBT2 in olmesartan medoxomil.
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Background: Epilepsy is a common neurological disorder. 30-40% of patients will continue to have seizures despite the use of antiepileptic drugs either alone or in combination. The present study is undertaken to evaluate the anticonvulsant activity of Acetazolamide (ACZ) in albino rats and its influence on anticonvulsant activity of sodium valproate.Methods: Albino rats (150-200gms) of male sex were randomly selected, from central animal facility, MMCRI, Mysore. They were divided into 6groups (per model) of 6 rats each, control group-normal saline 0.5ml, standard group-sodium valproate (300mg/kg), dose 1-ACZ (8.75mg/kg), dose 2-ACZ (17.5mg/kg) and dose 3-ACZ (35mg/kg), dose 4-ACZ (8.75mg/kg) with sodium valproate (150mg/kg). The anti-convulsant activity was screened using MES model and PTZ model.Results: Results were analysed by ANOVA followed by post hoc Fisher’s LSD test. The ACZ has shown anticonvulsant activity at the dose of 17.5mg/kg and 35mg/kg body weight and combination of ACZ 8.75mg/kg with sodium valproate 150mg/kg both in MES model and PTZ model. The anticonvulsant activity of ACZ was less when compared to Sodium Valproate in both MES model and PTZ model. The anticonvulsant activity of combination, ACZ 8.75mg/kg with Sodium valproate 150mg/kg was comparable and more significant when compared to standard drug alone in MES model and PTZ model.Conclusions: The ACZ has shown anticonvulsant activity in MES model and PTZ induced seizure model of epilepsy. This study has shown that ACZ potentiated the effect of sodium valproate and can be used as add on drug with sodium valproate in epilepsy.
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Mikania scandens, a twining herb that grows as a weed in India and Bangladesh is used as vegetables and is a good source of vitamin A, C, B complex, mikanin, sesquiterpenes, betasitosterin, stigmasterol and friedelin. The present communication reports CNS depressant activities with special emphasis to brain biogenic amines in mice. Ethanol extract of leaves of M. scandens (EEMS) was prepared by Soxhalation and analyzed chemically. EEMS potentiated sleeping time induced by pentobarbitone, diazepam and meprobamate and showed significant reduction in the number of writhes and stretches. EEMS caused significant protection against pentylene tetrazole-induced convulsion and increased catecholamines and brain amino acids level significantly. Results showed that EEMS produced good CNS depressant effects in mice.