Schinus molle: anatomy of leaves and stems, chemical composition and insecticidal activities of volatile oil against bed bug (Cimex lectularius)

Authors

Camila D. Machado, Universidade Estadual de Ponta Grossa
Vijayasankar Raman, University of Mississippi School of Pharmacy
Junaid U. Rehman, University of Mississippi School of Pharmacy
Beatriz H.L.N.S. Maia, Universidade Federal do Parana
Emanuelle K. Meneghetti, Universidade Federal do Parana
Valter P. Almeida, Universidade Estadual de Ponta Grossa
Rosi Z. Silva, Universidade Estadual de Ponta Grossa
Paulo V. Farago, Universidade Estadual de Ponta Grossa
Ikhlas A. Khan, University of Mississippi School of Pharmacy
Jane M. Budel, Universidade Estadual de Ponta Grossa

Document Type

Article

Publication Date

1-1-2019

Abstract

© 2019 by the authors The investigation of the constituents that were isolated from Turnera diffusa (damiana) for their inhibitory activities against recombinant human monoamine oxidases (MAO-A and MAO-B) in vitro identified acacetin 7-methyl ether as a potent selective inhibitor of MAO-B (IC50 = 198 nM). Acacetin 7-methyl ether (also known as 5-hydroxy-40, 7-dimethoxyflavone) is a naturally occurring flavone that is present in many plants and vegetables. Acacetin 7-methyl ether was four-fold less potent as an inhibitor of MAO-B when compared to acacetin (IC50 = 50 nM). However, acacetin 7-methyl ether was >500-fold selective against MAO-B over MAO-A as compared to only two-fold selectivity shown by acacetin. Even though the IC50 for inhibition of MAO-B by acacetin 7-methyl ether was ~four-fold higher than that of the standard drug deprenyl (i.e., SelegilineTM or ZelaparTM, a selective MAO-B inhibitor), acacetin 7-methyl ether’s selectivity for MAO-B over MAO-A inhibition was greater than that of deprenyl (>500- vs. 450-fold). The binding of acacetin 7-methyl ether to MAO-B was reversible and time-independent, as revealed by enzyme-inhibitor complex equilibrium dialysis assays. The investigation on the enzyme inhibition-kinetics analysis with varying concentrations of acacetin 7-methyl ether and the substrate (kynuramine) suggested a competitive mechanism of inhibition of MAO-B by acacetin 7-methyl ether with Ki value of 45 nM. The docking scores and binding-free energies of acacetin 7-methyl ether to the X-ray crystal structures of MAO-A and MAO-B confirmed the selectivity of binding of this molecule to MAO-B over MAO-A. In addition, molecular dynamics results also revealed that acacetin 7-methyl ether formed a stable and strong complex with MAO-B. The selective inhibition of MAO-B suggests further investigations on acacetin 7-methyl as a potential new drug lead for the treatment of neurodegenerative disorders, including Parkinson’s disease.

Relational Format

journal article

Recommended Citation

Machado, C. D., Raman, V., Rehman, J. U., Maia, B. H. L. N. S., Meneghetti, E. K., Almeida, V. P., Silva, R. Z., Farago, P. V., Khan, I. A., & Budel, J. M. (2019). Schinus molle: anatomy of leaves and stems, chemical composition and insecticidal activities of volatile oil against bed bug (Cimex lectularius). Revista Brasileira de Farmacognosia, 29(1), 1–10. https://doi.org/10.1016/j.bjp.2018.10.005

DOI

10.1016/j.bjp.2018.10.005