2. Academic Validation
  3. Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells

Design and synthesis of lupeol analogues and their glucose uptake stimulatory effect in L6 skeletal muscle cells

  • Bioorg Med Chem Lett. 2014 Jun 15;24(12):2674-9. doi: 10.1016/j.bmcl.2014.04.059.
Mohammad Faheem Khan 1,  Chandan Kumar Maurya 2,  Kapil Dev 3,  Deepti Arha 4,  Amit Kumar Rai 2,  Akhilesh Kumar Tamrakar 4,  Rakesh Maurya 5
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 2 Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 3 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
  • 4 Biochemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India.
  • 5 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: mauryarakesh@rediffmail.com.
PMID: 24813738 DOI: 10.1016/j.bmcl.2014.04.059
Abstract

Structure modifications of lupeol at the isopropylene moiety have been described via allylic oxidation using selenium dioxide. The antidiabetic efficacy of lupeol analogues were evaluated in vitro as glucose uptake stimulatory effect in L6 skeletal muscle cells. From all tested compounds, 2, 3, 4b and 6b showed significant stimulation of glucose uptake with respective percent stimulation of 173.1 (p <0.001), 114.1 (p <0.001), 98.3 (p <0.001) and 107.3 (p <0.001) at 10μM concentration. Stimulation of glucose uptake by these compounds is associated with enhanced translocation of glucose transporter 4 (GLUT4) and activation of IRS-1/PI3-K/AKT-dependent signaling pathway in L6 cells. Structure-activity relationship analysis of these analogues demonstrated that the integrity of α,β-unsaturated carbonyl and acetyl moieties were important in the retention of glucose uptake stimulatory effect. It is therefore proposed that naturally occurring lupeol and their analogues might reduce blood glucose, at least in part, through stimulating glucose utilization by skeletal muscles.

Keywords

Glucose uptake stimulation; Isopropylene moiety; Lupeol; Type 2 diabetes mellitus.

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