Synthesis of novel triterpenoid (lupeol) derivatives and their in vivo antihyperglycemic and antidyslipidemic activity

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 15; pp. 4463 - 4466
• Main Authors: Papi Reddy, K., Singh, A.B., Puri, A., Srivastava, A.K., Narender, T.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01-08-2009; Elsevier
• Subjects: Animals; Anti-Inflammatory Agents - chemical synthesis; Anti-Inflammatory Agents - pharmacology; Antidyslipidemic activity; Antihyperglycemic activity; Biological and medical sciences; Body Weight; Chemistry, Pharmaceutical - methods; Cricetinae; Diabetes Mellitus, Experimental - drug therapy; Drug Design; General and cellular metabolism. Vitamins; Glucose - metabolism; Hypoglycemic Agents - chemical synthesis; Hypoglycemic Agents - pharmacology; Hypolipidemic Agents - chemical synthesis; Hypolipidemic Agents - pharmacology; Lupeol ester derivatives; Medical sciences; Models, Chemical; Pentacyclic Triterpenes; Pharmacology. Drug treatments; Rats; Streptozocin; STZ-S model; Triglycerides - chemistry; Triterpenes - chemical synthesis; Triterpenes - pharmacology; Lupeol ester derivatives; Antihyperglycemic activity; Antidyslipidemic activity; STZ-S model; Endocrinopathy; Pentacyclic compound; Rat; Saturated compound; Lipids; Pyridine derivatives; Hypoglycemic agent; Structure activity relation; Dyslipemia; Chemical synthesis; Acylate; Nicotinic acid derivatives; Terpenoid; Diabetes mellitus; Rodentia; Benzene derivatives; Metabolic diseases; In vivo; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Animal; Triterpene; Hamster; Antilipemic agent
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.05.034

The triterpenoid, lupeol (1) has been isolated from the leaves extract of Aegle marmelos. Few novel derivatives (2–13) were synthesized from the naturally occurring lupeol (1) and screened for their antihyperglycemic activity (2–11) and antidyslipidemic activity (2–4 and 12–13). The derivative 4 lowered the blood glucose levels by 18.2% and 25.0% at 5h and 24h, respectively, in sucrose challenged streptozotocin induced diabetic rats (STZ-S) model at the dose of 100mg/kg body weight. The compound 4 also significantly lowered 40% (P <0.001) in triglycerides, 30% (P <0.05) in glycerol, 24% (P <0.05) in cholesterol quantity and also improved the HDL–cholesterol by 5% in dyslipidemic hamster model at the dose of 50mg/kg b.wt.