Epoxyquinophomopsins A and B from endophytic fungus Phomopsis sp. and their activity against tyrosine kinase
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Epoxyquinophomopsins A and B from endophytic fungus Phomopsis sp. and their activity against tyrosine kinase Elvira Hermawati1 · Suzany D. Ellita1 · Lia D. Juliawaty1 · Euis H. Hakim1 · Yana M. Syah1 · Hayato Ishikawa2 Received: 19 August 2020 / Accepted: 23 September 2020 © The Japanese Society of Pharmacognosy 2020
Abstract Two new quinone derivatives, epoxyquinophomopsins A (1) and B (2), were purified from the EtOAc extract of endophytic fungus Phomopsis sp isolated from Morus cathayana. The structures of both compounds were determined based on 1D and 2D NMR and mass spectral data, as well as by x-ray diffraction analysis for 1. Compounds 1 and 2 were screened against eight receptor- (RTKs) and eight non-receptor tyrosine kinases (nRTKs). Both compounds showed strong inhibitory properties against Bruton’s Tyrosine Kinase (nRTK) with their kinase activity were 19% and 20%, respectively. Only compound 1 that showed strong inhibitory properties against RTKs EGFR and HER-4 with its kinase activity were 16 and 15%, respectively. Thus, both compounds have potential as tyrosine kinase inhibitors. Keywords Epoxyquinophomopsin A · epoxyquinophomopsin B · Phomopsis sp. · Morus cathayana · Receptor tyrosine kinase · Non-receptor tyrosine kinase
Introduction Tyrosine Kinases (TKs) are enzymes that activate and regulate cell proliferation signaling pathways through phosphorylation of the tyrosine residue of the protein [1]. The phosphorylation causes changes in their enzymatic activity of the protein resulting in a specific biological event. Based on its function, PTKs can be divided into receptor tyrosine kinases (RTK) and non-receptor tyrosine kinase (nRTKs). Examples of the RTKs are EGFR, HER2, HER4 (epidermal growth factor receptor), IGF1R, InsR (insulin receptor), KDR (kinase insert domain receptor), PDGFR α, and PDGFR β (platelet-derived growth factor receptor) [2]. The nRTKs include ABL1 (Abelson tyrosine kinase), BRK (breast cancer kinase), FYNA, LCK (lymphocyte-specific Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11418-020-01454-1) contains supplementary material, which is available to authorized users. * Elvira Hermawati [email protected] 1
Organic Chemistry Division, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Indonesia
Department of Chemistry, Kumamoto University, Kuroki, 2‑39‑1, Chuo‑ku, Kumamoto 860‑8555, Japan
2
protein tyrosine kinase), LYNB (Lck/Yes-related novel tyrosine kinase), SRC (Src family), BTK (Bruton’s tyrosine kinase), and CSK (C-terminal Src kinase) [3]. Overexpression of these enzymes has been implicated in various diseases, including cancers. Therefore, finding active compounds as inhibitors RTKs and/or nRTKs are of interest to many researchers to find new candidates for anticancer agents [4]. Previously, we have reported a new isofuranonaphthoquinone derivative (i.e., epoxyquinophomopsin) from the EtOAc extract of the fermentation broth’s culture of endophytic fungus Phomopsis sp, which was iso
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