Multitargeted molecular docking and dynamics simulation studies of flavonoids and volatile components from the peel of Citrus sinensis L. (Osbeck) against specific tumor protein markers

Abstract

Citrus sinensis (L.) Osbeck (Rutaceae), commonly known as the sweet orange, is a popular and widely consumed fruit with several medicinal properties. The present study aimed to perform the in silico screening of 18 flavonoids and eight volatile components from the peel of C. sinensis against apoptotic and inflammatory proteins, metalloprotease, and tumor suppressor markers. Flavonoids obtained higher probabilities than volatile components against selected anti-cancer drug targets. Hence, the data from the binding energies against the essential apoptotic and cell proliferation proteins substantiate that they may be promising compounds in developing effective candidates to block cell growth, proliferation, and induced cell death by activating the apoptotic pathway. Further, the binding stability of the selected targets and the corresponding molecules were analyzed by 100 ns molecular dynamics (MD) simulations. Chlorogenic acid has the most binding affinity against the important anti-cancer targets iNOS, MMP-9, and p53. The congruent binding mode to different drug targets focused on cancer shown by chlorogenic acid suggests that it may be a compound with significant therapeutic potential. Moreover, the binding energy predictions indicated that the compound had stable electrostatic and van der Waal energies. Thus, our data reinforce the medicinal importance of flavonoids from C. sinensis and expand the need for more studies, seeking to optimize results and amplify the impacts of further in vitro and in vivo studies.

Communicated by Ramaswamy H. Sarma

Keywords:

• Anticancer
• Citrus sinensis
• flavonoids
• volatile compounds
• molecular docking
• molecular dynamics

Acknowledgements

GRG would like to thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-Brazil for their financial assistance (Process number - 150056/2020-6). GRG gratefully acknowledges CNPq/Brazil for providing a Post-Doctoral Junior (PDJ) fellowship under the supervision of Prof. Dr. LJQJr. The study is part of the research group Biotecnologia e Inovação Terapêutica - BioINOVATEC. The authors also acknowledge the Inter-University Centre for Bioscience and Bioinformatics Infrastructure Facility at the Department of Biotechnology and Microbiology, Dr. Janaki Ammal Campus, Kannur University, for providing computational facilities.

Disclosure statement

No potential conflict of interest was reported by the authors.

Author contributions

Conception and design: GRG, CSS, LJQJ, MTS, LS, and NFS; participation in experimental analysis: NFS, MTS, LS, RQG, GRG, SRG, CSS, AJ, LJQJ, and SAC; funding acquisition: LJQJ and GRG; project administration, LJQJ, and LC; supervision: LJQJ, MTS, LS and GRG; writing original draft: GRG, SRG, GS, RS, and VEH; manuscript editing: GRG, MH, LJQJ, RQG, and CSS. All authors have read and agreed to the published version of the manuscript.

Additional information

Funding

This project received financial support from Rajagiri College of Social Sciences (Autonomous), Kochi, India, in, the seed money category for minor faculty research projects (MRP).