ABSTRACT
New 1-substituted-biguanide derivatives 1-3 were synthesized by the reaction of 2,4-dimethoxyaniline, hydrazine and methylhydrazine with dicyandiamide in diluted hydrochloric acid. The resulting biguanide salts were fully characterized by spectroscopic methods. The synthesized compounds were screened for their anti-diabetic activity with standard metformin drug. Oral treatment of hyperglycemic rats with the synthesized biguanide derivatives (200 mg/kg/day) for 2 weeks significantly decreased the elevated blood glucose level. Oral administration of biguanide derivative 2 significantly decreased the level of total cholesterol. While, the triglycerides level was little decreased following administration of biguanide 1 as compared to hyperglycemic rats. Additionally, anti-diabetic properties towards liver function enzyme activities (AST and ALT) and kidney functions (urea and critinine) as well as histopathological studies relative to metformin hydrochloride were investigated and discussed.
Subject(s)
Biguanides/chemistry , Biguanides/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Insulin Resistance , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Biguanides/chemical synthesis , Blood Glucose , Cholesterol/blood , Creatinine/urine , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/pathology , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/therapeutic use , Liver/pathology , Male , Metformin/therapeutic use , Rats , Rats, Wistar , Triglycerides/blood , Urea/urineABSTRACT
A series of 3,4,5-trisubstituted 2(5H)-furanone derivatives was synthesized through one-pot reaction of amines, aldehydes and diethyl acetylenedicarboxylate. Silica sulfuric acid efficiently catalyzes the 3-component reaction to afford the corresponding 2(5H)-furanones in high yields. The synthesized compounds were tested against HEPG2, MCF7 and CACO tumor cell lines. The cytotoxic activity for the tested compounds showed that: ethyl 2-(4-fluorophenyl)-5-oxo-4-(phenylamino)-2,5-dihydrofuran-3-carboxylate exhibited significant antitumor activity against HEPG2 and MCF7 cell lines (IC50 values 0.002 and 0.002 µM, respectively) more than reference drug (IC50 0.007, 0.005 µM).
Subject(s)
4-Butyrolactone/analogs & derivatives , Aniline Compounds/chemical synthesis , Aniline Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , 4-Butyrolactone/chemical synthesis , 4-Butyrolactone/pharmacology , 4-Butyrolactone/toxicity , Aniline Compounds/toxicity , Cell Line, Tumor , Humans , Inhibitory Concentration 50 , Structure-Activity RelationshipABSTRACT
Reaction of 6-chloro-9-benzyl-8-(methylthio)purine 3 with primary amines afforded, the corresponding 6-(substitutedamino)purines 4a-g. The latter products when methylated with methyl iodide yielded smoothly N3-methyl purinium iodide salts 5a-f rather than the probable N1- and N7-derivatives. 9-Benzyl-3-methyl-6-(methylimino)-8-(methylthio)purine 8 was obtained upon treating the purinium iodide 5a with alkali. Most of the synthesized compounds were screened for their antitumor activity.
