Integrative approach based on LS-MS, LC-MS/MS, NMR, and in silico techniques for the rapid screening of COX-2 inhibitor alkaloids from Bocageopsis canescens (Benth.) R.E. Fr (Annonaceae)

Elzalina R. Soaresa*, Bruna R. de Limaa, Jessica B. Maciela, Hanna M. Rocha, Richardson A. de Almeidaa, Afonso D. L. de Souzaa, Felipe M. A. da Silvaa, Maria L. B. Pinheiroa

aDepartment of Chemistry, Federal University of Amazonas - UFAM, 69080-900 Manaus, AM, Brazil. *[email protected]

Since the beginning of time, the human relied on nature, in a predatory way, to obtain resources, causing the disappearance of an innumerable number of plant species. Some of these species remain unexplored, and their active principles are unknown, e.g. the Bocageopsis species, whose individuals are used in traditional medicine [1-2]. Previous studies point the Bocageopsis genus as a promising source of alkaloids, such as aporphine, proaporphine, oxoaporphine, benzilisoquinoline and β-carboline [3]. The use of integrative approaches that allow fast recognition of active principles, such as computational ones (Molecular docking), ambient ionization mass spectrometry (e.g. LS-MS), together with other modern techniques (UHPLC-DAD-MS/MS, 1D and 2D NMR) has become widely applied for the prospection of new substances with biological activity, along with the understanding of their mechanisms of action [4-5]. In order to screening cyclooxygenase-2 (COX-2) inhibitor alkaloids from B. canescens, a integrative approach was performed and eight alkaloids were tentatively identified (anonaine, nornucipherine, laurotetanine, isoboldine, asimilobine, N-methyl-laurotetanine, reticuline and stefarine). In silico analysis (molecular docking) has revealed hypothetical binding modes between the most active compounds (anonaine 1, nornuciferine 2 and laurotetanine 3) and the cyclooxygenase-2 enzyme (COX-2), supporting previous pharmacological studies [6] regarding alkaloids with cyclooxygenase-2 inhibitory potential.

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