DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF SOME NEW SUCCINIMIDE, 2-IMINOTHIAZOLINE AND OXAZINE DERIVATIVES BASED BENZOPYRONE AS ANTICONVULSANT AGENTS

Objective: The objective of the present study was to synthesize novel benzopyrone derivatives with potential and safer anticonvulsant activity.Methods: New benzopyrone derivatives have been synthesized and characterized by spectral and elemental analysis. These compounds tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens (phase 1), which are the most widely employed seizure models for early identification of new anticonvulsant agents. Phase 2 including, neurotoxicity screening and quantitative determination of the median effective dose (ED50), median lethal dose (LD50) and protective index (PI) for the active compounds from phase 1.Results: Compound 12b possessed potent anticonvulsant activity with ED50 values of 94.75 and 70.7 mg/kg in the MES and scPTZ screens respectively, and had LD50 value of 2546 mg/kg after intraperitoneal injection to mice, which provide compound 12b with a wide protective index of 26.87 and 36.01 for MES and scPTZ screens respectively compared to the reference drug Phenobarbital with PI of 12.16 and 20.08, respectively. In addition, compound 12b exhibited mild neurotoxicity at the maximum administrated dose (200 mg/kg).Conclusion: Compound 12b possessed broad spectrum activity for the treatment of all types of seizures, with a wide protective index compared to Phenobarbital. Consequently, compound 12b can be selected as a new bio candidate lead for further study.Keywords: Benzopyrone, Succinimide, 2-Iminothiazoline, Oxazine; Anticonvulsant

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF–MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract’s effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF–MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2′-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress

Chemical Profile of Cyperus laevigatus and Its Protective Effects against Thioacetamide-Induced Hepatorenal Toxicity in Rats

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF–MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract’s effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF–MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2′-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress