Akademik Veri Yönetim Sistemi
BAŞBINAR Y. (Yürütücü), SEYHAN S., SUCU S., BERRAK B.
Yükseköğretim Kurumları Destekli Proje, 2023 - 2024
Colorectal cancer (CRC) is the
third most commonly diagnosed cancer and the second leading cause of
cancer-related deaths worldwide [1]. TAM tyrosine kinase family is obtained
from three proteins: Tyro3, Axl, and MerTK. TAM receptors are overexpressed in
both CRC cells and tissues and these receptors have become potential
therapeutic targets for CRC [2]. Natural compounds are metabolites that
organisms synthesize and secrete for self-defense and are already used in
cancer therapy [3]. Genus Caulerpa, marine macroalgae, has 36 different
secondary metabolites to protect themselves from pathogens. The aim of the
study is to investigate the efficiency of marine-sourced natural compounds
against TAM tyrosine kinase family receptors by in-silico approaches. The
receptors (Axl and Mertk) were obtained from Protein Data Bank (Axl PDBID:
5U6B, Mertk PDBID: 7AAY). SwissModel was used for the modeling of Tyro3. The
receptors were prepared using AutoDock Tools-1.5.6. The most common secondary
metabolites (13 of 36 compounds) of the marine macroalgae, Caulerpa,
were obtained from PubChem. AutoDock Vina was used for molecular docking
studies. According to the results, racemosin C and monomethyl caulerpinate had
the highest binding energies against TAM tyrosine kinase receptors. The binding
energies of racemosin C were found as -9.2, -9.9 and -10.3 kcal/mol for Tyro3,
Axl, and Mertk, respectively. The binding energies of monomethyl caulerpinate
were found as -9.1, -9.5 and -9.5 kcal/mol for Tyro3, Axl, and Mertk,
respectively. In conclusion, TAM tyrosine kinase receptors are of great
importance for colorectal cancer treatment. Racemosin C and monomethyl caulerpinate
could be evaluated as important molecules against these receptors.
Acknowledgement: This study was
funded by Dokuz Eylül University Scientific Research Projects (Grant number: TLO-2023-3094)