In-silico Approach for Evaluation of Antimalarial Potential of Costunolide Synthase Enzyme and Sesquiterpene Lactones from Cichorium intybus

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 in the biosynthesis pathway of sesquiterpene lactones, which is thought to give the plant 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 the more evidences and explanations 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.