Synthesis of propiophenone derivatives as new class of antidiabetic agents reducing body weight in db/db mice

Atul Kumar; Siddharth Sharma; Lalit Prakash Gupta; Pervez Ahmad; Swayam Prakash Srivastava; Neha Rahuja; A K Tamrakar; Arvind K Srivastava

doi:10.1016/j.bmc.2011.12.027

Synthesis of propiophenone derivatives as new class of antidiabetic agents reducing body weight in db/db mice

Bioorg Med Chem. 2012 Mar 15;20(6):2172-9. doi: 10.1016/j.bmc.2011.12.027. Epub 2011 Dec 24.

Authors

Atul Kumar¹, Siddharth Sharma, Lalit Prakash Gupta, Pervez Ahmad, Swayam Prakash Srivastava, Neha Rahuja, A K Tamrakar, Arvind K Srivastava

Affiliation

¹ Medicinal and Process Chemistry Division, Central Drug Research Institute, Council of Scientific and Industrial Research, Lucknow 226 001, India. dratulsax@gmail.com

PMID: 22341243
DOI: 10.1016/j.bmc.2011.12.027

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Glucose / drug effects
Diabetes Mellitus, Experimental / blood
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Experimental / metabolism
Eating / drug effects
Hypoglycemic Agents / chemical synthesis
Hypoglycemic Agents / chemistry*
Hypoglycemic Agents / pharmacology
Hypoglycemic Agents / therapeutic use*
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 / chemistry*
Propiophenones / pharmacology
Propiophenones / therapeutic use*
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors
Protein Tyrosine Phosphatase, Non-Receptor Type 1 / metabolism
Rats
Rats, Sprague-Dawley
Rats, Wistar
Streptozocin
Weight Loss / drug effects*

Substances

Blood Glucose
Hypoglycemic Agents
Hypolipidemic Agents
Lipids
Propiophenones
Streptozocin
Protein Tyrosine Phosphatase, Non-Receptor Type 1