Title:In-silico Approach for Evaluation of Antimalarial Potential of Costunolide
Synthase Enzyme and Sesquiterpene Lactones from Cichorium intybus
Volume: 20
Issue: 1
Author(s): Abhishek Pathak, Sunita Arora, Apoorv Tiwari, Kurma Dev Krishna, S.P. Singh and Gohar Taj*
Affiliation:
- Department of Molecular Biology and Genetic Engineering, College of Basic
Sciences and Humanities, GBPUA&T, Pantnagar, Uttarakhand, 263145, India
Keywords:
Sesquiterpene lactones, lactucin, lactucopicrin, antimalarial agent, molecular docking, plasmepsin II.
Abstract:
Background: Cichorium intybus is a perennial herb in the Asteraceae family that has significant
ethano-medical properties and is utilized in Ayurveda and Unani therapy. The enzyme costunolide
synthase contributes to the biosynthesis pathway of sesquiterpene lactones, which is thought to provide
the plant with antimalarial action.
Methods: This work uses several in-silico techniques along with docking experiments to show the
structural and physiochemical characteristics of the enzyme costunolide synthase. Costunolide synthase
protein interacts with lactucin and lactucopicrin with lower energy interactions of -4.99 kcal/mol for
total 3 hydrogen bonds and -6.55 kcal/mol for total 2 hydrogen bonds, respectively. One domain
named CYP 450 has been found, which catalyzes a variety of oxidative reactions of a large number of
structurally different compounds that are both endogenous and exogenous from all major domains of
life. The mitochondrial cellular localization of protein was revealed with a maximum score of 1.833.
Results: The phylogenetic study revealed that the enzyme costunolide synthase from Cichorium intybus
has a greater resemblance to Cichorium endivia and Lactuca sativa of costunolide synthase. Molecular
docking findings of sesquiterpene lactones (lactucin and lactucopicrin) with Plasmepsin II protein
of P. falciparum parasites after clinical trials with sesquiterpene lactones may give more evidence
and explanation for the active involvement of lactucin and lactucopicrin as an antimalarial compound.
Conclusion: This research will be used in future wet-lab studies to figure out how the costunolide synthase
enzyme regulates sesquiterpene lactones and to investigate additional regulatory enzyme involved
in the synthesis of sesquiterpene lactones.
