The inhibitory effect of common food spices bioactive compounds against KRAS G12C and KRAS G12D: an in-silico approach

Abstract

More than 19 percent of all human cancer cases globally express mutant RAS proteins, which are the most frequently altered oncogenic proteins. Targeting cancer cells becomes difficult because these oncogenic proteins and cancer cells that are driven by Ras mutation show very aggressive traits. KRAS is the most expressed among the three isoforms of Ras mutation, which usually occur at position 12. KRAS G12C and KRAS G12D are common types of KRAS that have been proven difficult to target for many years. In recent times, many studies started to show that a lot of food spices possess strong anticancer properties that can target many cancer cells. Therefore, computational methods to access the anticancer properties of some selected compounds that are present in common food spices against KRAS G12C and KRAS G12D in their inactive GDP-bound state. These compounds were molecularly docked with standard drugs after their ADMET screening revealed their druglikeness. Chlorogenic acid and Rosmarinic acid displayed better binding affinity to the targets than all other drugs studied in this research. Molecular dynamics simulation was used to verify this compound's stability. Therefore, after extensive experimental effort, it is most likely that Rosmarinic acid would be effective as a KRAS G12C medicine.