ABSTRACT
A series of novel chromone derivatives of (N-(4-oxo-2-(trifluoromethyl)-4H-chromen-6-yl) benzamides) were synthesized by treating 7-amino-2-(trifluoromethyl)-4H-chromen-4-one with K2CO3 and/or NaH, suitable alkyl halides and acetonitrile and/or 1,4-dioxane. The obtained products are in high yields (87 to 96%) with various substituents in short reaction times with no more by-products and confirmed by FT-IR, 1H, and 13C-NMR Spectral data. The in vitro cytotoxic activity was examined against two human cancer cell lines, namely the human lung adenocarcinoma (A-549) and the human breast (MCF-7) cancer cell line. Compound 4h showed promising cytotoxicity against both cell lines with IC50 values of 22.09 and 6.40 ± 0.26 µg/mL respectively, compared to that of the standard drug. We also performed the in vitro antioxidant activity by DPPH radical, hydrogen peroxide, NO scavenging, and total antioxidant capacity (TAC) assay methods, and they showed significant activities. The possible binding interactions of all the synthesized chromone derivatives are also investigated against selective pharmacological targets of human beings, such as HERA protein for cytotoxic activity and Peroxiredoxins (3MNG) for antioxidant activity which showed closer binding free energies than the standard drugs and evidencing the above two types of activities.
Subject(s)
Antineoplastic Agents , Antioxidants , Benzamides , Molecular Docking Simulation , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Antioxidants/chemistry , Benzamides/pharmacology , Benzamides/chemistry , Benzamides/chemical synthesis , MCF-7 Cells , A549 Cells , Chromones/chemistry , Chromones/pharmacology , Chromones/chemical synthesis , Cell Line, Tumor , Structure-Activity RelationshipABSTRACT
AIM: The aim of the present study is to evaluate the antiepileptic activity of chloroform extract of aerial parts of Acalypha fruticosa in mice. MATERIALS AND METHODS: The antiepileptic activity of chloroform extract of A. fruticosa at the doses of 30, 100 and 300 mg/kg, p.o. was evaluated by maximum electroshock (MES), pentylenetetrazole (PTZ) and isoniazid (INH)-induced convulsions in mice. Statistical analysis was carried out by one-way analysis of variance followed by Dunnett's test. RESULTS: In MES method, the chloroform extract significantly protected the mice from convulsions induced by electroshock method in a dose-dependent manner and exhibited more activity at the dose of 300 mg/kg when compared with diazepam treated animals. In PTZ method, the extract inhibited convulsions in mice potent than phenobarbitone sodium. In INH method, it delayed the latency of convulsions in mice in a dose-dependent manner but failed to protect the mice against mortality. CONCLUSION: The chloroform extract exhibited significant and dose-dependent antiepileptic activity, which may be due to the presence of antioxidant principles like flavanoids.
