Solation and characterization of compounds from the bark of Ochreinauclea maingayi (Hook. F.) RISDS. (Rubiaceae) with the aid of LCMS/MS molecular networking and their anticholinesterase activity / Norfaizah Osman

Norfaizah , Osman (2023) Solation and characterization of compounds from the bark of Ochreinauclea maingayi (Hook. F.) RISDS. (Rubiaceae) with the aid of LCMS/MS molecular networking and their anticholinesterase activity / Norfaizah Osman. PhD thesis, Universiti Malaya.

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Abstract

A phytochemical investigation of the dichloromethane crude extract (DCE) from the bark of Ochreinauclea maingayi was performed with the aid of LCMS/MS-based molecular networking (MN) to accelerate the research workflow. MN permits extracting information on related molecules from the DCE based on the similarity of their fragmentation MS/MS spectra. In this study, one new indole alkaloid, dihydrodeglycocdambine (149), together with other twenty-one known compounds, was successfully identified from MN analysis. With the aid of LCMS/MS molecular networking, 149 was successfully isolated and purified from the bark of O. maingayi using the chromatography technique, together with sixteen knows compounds; neonaucline(5), naucledine (6), harmane (7), naulafine (33), cadambine (35), norharmane (124), methyl 9H-β-carboline-4-carboxylate (150), 1,2,3,4 tetranorharmane-1-one (151), cinnamamide (152), benzamide (153), scopoletine (154), 4′-hydroxyacetophenone (155), decarboxyportentol acetate (156), scoparone (157), 2’-hydroxy-3’-methoxyacetophenone (158) and hexyl p-coumarate (159). All structures were elucidated using spectroscopic methods; UV, IR, NMR and LCMS. The DCE of the bark of O. maingayi has been tested for butyrylcholinesterase (BChE) inhibitory assay inhibited moderately with more than 54 % with 100 μg/mL. Further evaluation showed that fractions 7 and 9 could inhibit the BChE at more than 80 % at 100 μg/mL. Both fractions yielded three compounds: harmane (7), naucledine (6) and dihydrodeglycocadambine (149). Naucledine (6) was the most potent BChE inhibitor with an IC50 value of 22.08 μM followed by harmane (7) and dihydrodeglycocadambine (149) (23.96 and 30.32 μM, respectively). According to the kinetic study, BChE was inhibited by 6 in a mixed mode type. A molecular docking (MD) iv analysis showed that 6 docked deep into the bottom gorge of BChE, interacted with Ser 198 and His 438 at the catalytic site, and formed hydrogen bonds with Gly 116 in an oxyanion hole.

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