- 作者: Henry J Tsai; Shan-Yen Chou
- 作者服務機構: Pharmaceutical R&D Program, Development Center for Biotechnology, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
Background :
Diabetes Mellitus is a chronic disease and many patients of which require frequent
subcutaneous insulin injection to maintain proper blood glucose levels. Due to the
inconvenience of insulin administration, an orally active insulin replacement has long
been a prime target for many pharmaceutical companies. Demethylasterriquinone
(DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported
to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db)
mice; however, the cytotoxicity associated with the quinone moiety has not been
addressed thus far.
Methods :
A series of hydroxyfuroic acid compounds were synthesized and tested for their
efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster
ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth
factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this
study.
Results and Conclusions :
This study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid
compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potentas compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human
insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a
moderate inhibitor to EGF receptor. Structure and activity relationship of the
prenylindole moiety to insulin receptor activation is discussed. - 中文關鍵字: --
- 英文關鍵字: --