Loo Kong Yong, Leong Kok Hoong, Sivasothy Yasodha, Ibrahim Halijah, Awang Khalijah
Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Center for Natural Product and Drug Discovery (CENAR), Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
Chem Biodivers. 2019 Jun;16(6):e1900032. doi: 10.1002/cbdv.201900032. Epub 2019 May 9.
The inhibition of carbohydrate-hydrolyzing enzymes in human digestive organs is crucial in controlling blood sugar levels, which is important in treating type 2 diabetes. In the current study, pahangensin A (1), a bis-labdanic diterpene characterized previously in the rhizomes of Alpinia pahangensis Ridl., was identified as an active dual inhibitor for α-amylase (IC =114.80 μm) and α-glucosidase (IC =153.87 μm). This is the first report on the dual α-amylase and α-glucosidase inhibitory activities of a bis-labdanic diterpene. The Lineweaver-Burk plots of compound 1 indicate that it is a mixed-type inhibitor with regard to both enzymes. Based on molecular docking studies, compound 1 docked in a non-active site of both enzymes. The dual inhibitory activity of compound 1 makes it a suitable natural alternative in the treatment of type 2 diabetes.
抑制人体消化器官中的碳水化合物水解酶对于控制血糖水平至关重要,这在治疗2型糖尿病中具有重要意义。在当前的研究中,曾在彭亨月桂(Alpinia pahangensis Ridl.)根茎中鉴定出的双-labdanic二萜类化合物彭亨月桂素A(1),被确定为α-淀粉酶(IC =114.80 μm)和α-葡萄糖苷酶(IC =153.87 μm)的活性双重抑制剂。这是关于双-labdanic二萜类化合物具有双重α-淀粉酶和α-葡萄糖苷酶抑制活性的首次报道。化合物1的Lineweaver-Burk图表明,它对于这两种酶而言都是混合型抑制剂。基于分子对接研究,化合物1对接在这两种酶的非活性位点。化合物1的双重抑制活性使其成为治疗2型糖尿病的合适天然替代品。