For drug development of anti-diabetic research, we used the bioactive compound isosteviol, hydrolyzed from stevioside, as lead compound and chemical modified its structure to search a more potent drug. We have synthesized a serial isosteviol derivatives 4~29, and derivatives 9, 11, and 13~15 shown most anti-diabetic bioactivities than others. However, their bioavailability is low. Base on increasing the bioavailability, we modified diester, inositol, tetrazole and amide substituents at the C19 of carboxylic acid and oxime ether and amine at the C16 of carbonyl group, and then evaluate bioactivity of these derivatives. In this drug design, using “twin drug approach” to produce a more potent and/or more selective drug is a common strategy. It needs two years to complete this project. First year, we will synthesize 50 compounds of C19 diester/inositol/tetrazol/amide C16 oxime ether/alkylamine to evaluate their anti-diabetic bioactivity. Second year, we will synthesize 50 compounds of twin drug to obtain more potent anti-diabetic agents. We will anticipate these isosteviol derivatives are active compounds and determine the structure and activity relationship of the series isosteviol derivatives from the results of bioassay.
|Effective start/end date||8/1/13 → 7/31/14|
- twin drug