Assessment of hypolipidaemic activity of three thiazolidin-4-ones in mice given high-fat diet and fructose.
Three 4-thiazolidinones, two with nicotinamide (NAT1 and NAT2) and one with 4-chlorophenoxyacetamide (PAT1) side chains were evaluated for their hypolipidaemic, hypoglycaemic activity in Swiss albino mice fed a high-fat diet along with fructose administered in drinking water. NAT1 and PAT caused reduction of elevated triglycerides, cholesterol and glucose; NAT2 was effective only against triglycerides. Nicotinamide side chain might have contributed to the lipid lowering effect of both NAT1 and NAT2, but the bulky group of the latter could have affected proper binding to the receptor sites, making it ineffective against elevated cholesterol. On the other hand, the 4-chlorophenoxyacetamide side chain of PAT might have exerted powerful hypolipidaemic activity, despite the bulky substitution at C2. As antioxidants, NAT2 and PAT1 showed superior activity, compared to NAT1. The thiazolidinone ring might be responsible for the lipid lowering effect, which is however, modified by the type of substitutions at C2 and N of the ring. Detailed study is warranted to explain the mechanism of action of these compounds as also to make more potent ones.
Nampurath
Gopalan Kutty
GK
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Madhava Nagar, Manipal, Karnataka, India. ng.kutty@manipal.edu
Mathew
Suma P
SP
Khanna
Vivek
V
Zachariah
Robby T
RT
Kanji
Suman
S
Chamallamudi
Mallikarjuna Rao
MR
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005632:Fructose / Q000008:administration & dosage*; D006016:Glycolates / Q000008:administration & dosage* / Q000737:chemistry; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D051379:Mice; D015394:Molecular Structure; D009525:Niacin / Q000008:administration & dosage; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000737:chemistry; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D004041:Dietary Fats; D006016:Glycolates; D000960:Hypolipidemic Agents; C524550:N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxo-thiazolidin-3-yl)-nicotinamide; C528865:N-(2-(3,5-di-tert-butyl-4-hydroxyphenyl)-4-oxothiazolidin-3-yl-(4-chlorophenoxy))acetamide; C528863:N-(2-(4-methoxyphenyl)-4-oxothiazolidin-3-yl)nicotinamide; D045162:Thiazolidinediones; D014280:Triglycerides; D009536:Niacinamide; D009525:Niacin; D005632:Fructose; D002784:Cholesterol