Potential derivatives in the treatment of diabetes and cancer
Within the framework of the international cooperation mission: "Design, synthesis and evaluation of alpha-glucosidase inhibitory activity of some triterpenoid arylidene derivatives", two research groups from the Institute of Chemistry, Vietnam Academy of Science and Technology and UFA Research Institute of Chemistry, Russian Academy of Sciences, jointly studied the synthesis and evaluation of the activity of 231 leads export.
Using the original approach and using modern methods of organic chemistry, the team of Russian scientists synthesized triterpenoid derivatives containing the arylidene group. In addition, triterpenoid hybrids with oxo-, azaheterocyclic (indolo-, oxazolo-, quinolono-, pyrazolo-) and trytophanamide derivatives containing the indole group have also been synthesized.
For the derivatives obtained, the team of scientists on the Vietnamese side led by Dr. Nguyen Thi Thu Ha, Institute of Chemistry, led the team that studied the inhibitory activity of α-glucosidase invitro. Based on the screening results, both research groups analyzed the role of different triterpenoid frameworks and functional groups in the expression of antidiabetic activity, identified structural-active patterns using virtual screening methods in silico, computer-aided simulations, and selected potential compounds with IC50 values at nM concentrations to study diabetes in experimental animals in vivo. The Vietnamese research team also investigated antibacterial, antioxidant, cytotoxic activity, inhibition of NO production on Raw 264.7 cell line and inhibition of acetylcholinesterase enzyme of synthesized triterpenoid derivatives.
Based on the experimental evaluation of the α-glucosidase inhibitory activity of 231 compounds, the two research groups agreed to select 24/231 typical samples with strong α-glucosidase inhibitory effects (IC50 < 1 μg/ml) to continue evaluating other biological activities. These compounds are synthesized with high efficiency, so multiple bioactivity evaluations can be performed on the invitro model as well as the invivo model. Dr. Nguyen Thi Thu Ha and colleagues evaluated toxic activity on 4 cancer cell lines of 24 compounds. In particular, A-50-furf compound has strong activity on all 4 cancer cell lines with IC50 values from 4.0±0.1 to 9.58±0.26 μg / ml. The compound 3NH2-M-2 is highly active and selective on Hep-G2 liver cancer strains with an IC50 value of 1.25±0.05 μg/ml.
Enzymatic Kinetics Studies and Molecular Docking Model of Compound 45 (TEV-056)
The NO molecule is known to play a central role in inflammatory and immune responses. The compound with anti-inflammatory activity will have the ability to reduce the secretion of NO by cells. Diabetes is one of the causes of increased secretion of inflammatory compounds and immune dysfunction in the body. Of the 24 compounds with potent inhibitory activity of the enzyme α-glucosidase, 10 out of 24 compounds have potential in research to develop anti-inflammatory agents due to their strong inhibitory activity of NO production. This is a success to expand the research direction of anti-inflammatory active ingredients on the basis of substances that inhibit the enzyme α-glucosidase. These results are the scientific basis for Vietnam and Russia to continue to carry out research on the synthesis of bioactive derivatives from the triterpenoid framework in particular and the framework of natural origin in general, as well as further tests in mouse models for potential compounds in the future.
The research team has published 06 articles in SCI/SCIE journal, 01 article in VAST1 journal and contributed to training 01 pharmacist. With the success of the research results, the task was classified as excellent by the Acceptance Council of Vietnam Academy of Science and Technology.
Translated by Phuong Ha
Link to Vietnamese version
