ABSTRACT
A series of propiophenone derivatives (6-23) have been synthesized and evaluated for their in vivo antihyperglycemic activities in sucrose loaded model (SLM), sucrose challenged streptozotocin (STZ-S) induced diabetic rat model and C57BL/KsJ db/db diabetic mice model. Compound 15 and 16 were emerged as potent antihyperglycemics and lipid lowering agents. These compounds (15, 16) further validate the potency by reducing body weight and food intake in db/db mice model. Possible mechanism of action for the propiophenone derivatives was established by the evaluation in various in vitro models. Interestingly some of the compounds were efficiently inhibiting PTP-1B.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/therapeutic use , Propiophenones/chemistry , Propiophenones/therapeutic use , Weight Loss/drug effects , Animals , Blood Glucose/drug effects , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Eating/drug effects , Hypoglycemic Agents/chemical synthesis , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/chemical synthesis , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Lipids/blood , Male , Mice , Mice, Inbred C57BL , Propiophenones/chemical synthesis , Propiophenones/pharmacology , Protein Tyrosine Phosphatase, Non-Receptor Type 1/antagonists & inhibitors , Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism , Rats , Rats, Sprague-Dawley , Rats, Wistar , StreptozocinABSTRACT
A new series of 1,3-biarylsulfanyl derivatives (homodibenzyl core motif) have been designed and synthesized as new estrogen receptor ligands by chopping benzothiophene core of raloxifene to engender seco-raloxifene scaffold. All the synthesized compounds were screened for anti-proliferative, anti-osteoporotic, and anti-implantation activity. Compounds (35, 36) having basic amino anti-estrogenic side chain were exhibiting potential anti-proliferative activity in MCF-7, MDA-MB-231 and ishikawa cell lines. Some of the synthesized compounds having homodibenzyl motif (5, 8, 10) have shown moderate anti-osteoporotic activity.
