Computational Study of Lactucine and its Derivatives to Investigate its
Anti-cancerous Properties Targeting Apoptosis-inducing Protein
Authors: Arya Mamta , Tiwari Apoorv , Singh Dev Bukhsh , Taj Gohar 
Published: February 2023

Background:

Lactucine is related to the sesquiterpene lactone group of naturally occurring
compounds and has a variety of pharmacological effects including anticancer properties found in Chicory,
Wormwood, Laurus nobilis, Pyrethrum, Chamomile, etc. Lactucine has an anticancer effect which may
induce apoptosis in cancerous cells and protect other cells from getting infected.

Objective:

In this study, Lactucine and its derivatives were screened, and performed their in silico docking
study with the proteins involved in the apoptosis-inducing effect in human leukemia cancer.

Methods:

The three-dimensional structure of lactucine and its derivatives were retrieved in the SDF format.
Active sites of protein structures were determined by Sitemap. LigPrep module was used for geometrical
refining of chemical structures of lactucine and its derivatives. The protein preparation wizard of
Maestro (Schrodinger) was used for protein preparation. From the receptor-complex structure, the cocrystallized
ligands were removed from the active site position of the receptor chain. All ligands were docked
using default Glide settings for a grid centered on the ligand and structure. Flexible docking was performed
using the extra precision (XP) feature of Glide module. The best docking poses for the lactucine
and their derivatives were selected based on their docking score. The ADMET properties of lactucine 15-
oxalate have been predicted by admetSAR software.

Results:

Proteins and ligands three-dimensional structures were retrieved from PDB and Pubchem databases,
respectively. All lactucine derivatives suitably docked on the apoptosis-inducing proteins with
ample Glide scores Lactucin 15-oxalate interacts with proteins which are responsible for apoptosis with a
maximum of six H-bonds. Other types of interactions are also involved, like Pi-cation, Pi-Pi stacking, salt
bridges, and halogen bonds. Protein CDK-4 has shown the highest number of H-bond (LYS142 salt
bridges), ALA16, VAL14, ASP99, LYS35, TYR17, and ASN145) with the Lactucin 15-oxalate. ADMET
properties of lactucin 15-oxalate met with the criteria of being eligible to be a novel drug for the treatment
of human leukemia cancer. The Dock score of both the Dasatinib drug and the lactucine-15-oxalate with
the apoptosis-inducing protein stipulates that the selected ligand has equitable interaction with the target
proteins.

Conclusion:

In this study, lactucine derivatives were docked with apoptosis-inducing proteins for the
prediction of its anticancer effect. Lactucin15-oxalate has shown the highest binding affinity for the
CDK-4 target and can be used as a lead compound for cancer treatment. Glide and Dock score for docking
of lactucin 15-oxalate with CDK-4, well as the number of hydrogen bonding, is in agreement to use
this ligand for study. These in silico results are valuable to proceed with the in vitro and in vivo studies
related to the anti-cancer role of lactucin 15-oxalate.