Page 109 - Pharma News Letter - Vol2 Issue 1

Research Publications

Repurposing Synthetic Congeners Of A Natural Product Aurone
Unveils A Lead Antitumor Agent Inhibiting Folded P-Loop
Conformation Of Met Receptor Tyrosine Kinase

Pharmaceuticals. 2023; 16(11): 1597.
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Ahmed H. E. Hassan, Cai Yi Wang, Cheol Jung Lee, Hye Rim Jeon, Yeonwoo Choi,
Suyeon Moon, Chae Hyeon Lee, Yeon Ju Kim, Soo Bin Cho, Kazem Mahmoud, Selwan

M El-Sayed, Sang Kook Lee, Yong Sup Lee

Abstract

A library of 24 congeners of the natural product sulfuretin were evaluated against nine panels
representing nine cancer diseases. While sulfuretin elicited very weak activities at 10 µM
concentration, congener 1t was identified as a potential compound triggering growth inhibition
of diverse cell lines. Mechanistic studies in HCT116 colon cancer cells revealed that congener
1t dose-dependently increased levels of cleaved-caspases 8 and 9 and cleaved-PARP, while it
concentration-dependently decreased levels of CDK4, CDK6, Cdc25A, and Cyclin D and E
resulting in induction of cell cycle arrest and apoptosis in colon cancer HCT116 cells. Mechanistic
study also presented MET receptor tyrosine kinase as the molecular target mediating the anticancer
activity of compound 1t in HCT116 cells. In silico study predicted folded p-loop conformation
as the form of MET receptor tyrosine kinase responsible for binding of compound 1t. Together,
the current study presents compound 1t as an interesting anticancer lead for further development.

Reference:

https://doi.org/10.3390/ph16111597

Vol. 2 - Issue 1 109