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ARS Home » Southeast Area » Oxford, Mississippi » Natural Products Utilization Research » Research » Publications at this Location » Publication #370820
Research Project: Discovery and Development of Natural Products for Pharmaceutical and Agrochemical Applications II

Location: Natural Products Utilization Research

Title: FOXO signal activating alkaloids isolated from Ochrosia elliptica leaf cultivated in Egypt

Author
item LABIB, ROLA - Ain Shams University Of Cairo
item ZULFIQAR, FAZILA - University Of Mississippi
item IBRAHIM, MOHAMED - University Of Mississippi
item BALACHANDRAN, PREMALATHA - University Of Mississippi
item ZHANG, JIN - University Of Mississippi
item ROSS, SAMIR - University Of Mississippi

Submitted to: Medicinal Chemistry Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/10/2019
Publication Date: 7/22/2019
Citation: Labib, R.M., Zulfiqar, F., Ibrahim, M.A., Balachandran, P., Zhang, J., Ross, S.A. 2019. FOXO signal activating alkaloids isolated from Ochrosia elliptica leaf cultivated in Egypt. Medicinal Chemistry Research. 28:1628-1632. https://doi.org/10.1007/s00044-019-02399-1.
DOI: https://doi.org/10.1007/s00044-019-02399-1

Interpretive Summary: A new yohimbine type alkaloid N-methylarcinine, and the known alkaloid, holeinine , have been isolated from the methanolic leaf extract of Ochrosia elliptica. Their structures were elucidated via Nuclear Magnetic Resonance (NMR) data, as well as High Resolution Electrospray Ionization Mass Spectrometry (HRESIMS) spectra. These two alkaloids are very different in activity from previously reported class type alkaloids, where they showed weak cytotoxic activity against K-562 leukemia cells while other compounds from this class were highly toxic in nature. Interestingly, holeinine (2) showed unique induction of the Forkhead box O (FOXO) expression, a cancer signaling pathway. This compound could be a candidate for drug development after the determination of its therapeutic efficacy and more mechanistic studies need to be evaluated.

Technical Abstract: A new yohimbine type alkaloid N-methylarcinine (1), and the known alkaloid, holeinine (2), have been isolated from the methanolic leaf extract of Ochrosia elliptica grown in Egypt. The structures of the isolated metabolites were elucidated via 1D and 2D NMR data, as well as High Resolution Electrospray Ionization Mass Spectrometry (HRESIMS) spectra and the spectral data were compared with the existing data available from literature. These two alkaloids are very different in activity from previously reported class type alkaloids, where they showed weak cytotoxic activity against K-562 leukemia cells while other compounds from this class were highly toxic in nature. Interestingly, holeinine (2) showed unique induction of the Forkhead box O (FOXO) expression, a cancer signaling pathway. FOXO is involved in the expression of death receptor ligands, such as tumor necrosis factor (TNF) apoptosis ligand, where its activation plays a critical role in tumor suppression. As several anticancer leads targeting FOXO signaling gain more attention, this compound could be a candidate for drug development after the determination of its therapeutic efficacy and more mechanistic studies need to be evaluated.