Dual High-Resolution α-Glucosidase and PTP1B Inhibition Profiling Combined with HPLC-PDA-HRMS-SPE-NMR Analysis for the Identification of Potentially Antidiabetic Chromene Meroterpenoids from Rhododendron capitatum

Abstract

Thirteen previously undescribed chromene meroterpenoids, capitachromenic acids A−M (3−6, 7a, 7b, 8a, 8b, 9a, 9b, 10a, 10b, and 11b), were identified from an ethyl acetate extract of Rhododendron capitatum, using dual high-resolution αglucosidase and PTP1B inhibition profiling in combination with HPLC-PDA-HRMS-SPE-NMR. In addition, one known chromene meroterpenoid, daurichromenic acid (15), and its biosynthetic precursor, grifolic acid (12), two C-methylated flavanones, (2S)-5,7,4′-trihydroxy-8-methylflavanone (1) and farrerol (2), and two triterpenoids, oleanolic acid (14a) and ursolic acid (14b), were identified. New structures were elucidated by extensive 1D and 2D NMR analysis, and absolute configurations of new chromene meroterpenoids were assigned by analysis of their ECD spectra on the basis of the empirical chromane helicity rule and from Rh 2 (OCOCF 3 ) 4 -induced ECD spectra by applying the bulkiness rule. Compounds 5, 9a, 9b, 12, and 15 showed α-glucosidase inhibitory activity with IC 50 values ranging from 8.0 to 93.5 μM, while compounds 3, 5, 8b, 9a, 9b, 10b, 11b, 12, and 15 showed PTP1B inhibitory activity with IC 50 values ranging from 2.5 to 68.1 μM.

Synthesis of Chalcogenylchromenes through Cyclization of Propargylic Aryl Ethers

“…Chromenes and their derivatives represent an important structural unit found in several natural products and compounds with important biological activities, such as anticancer, antidiabetic, cardiovascular, and anti-inflammatory activity . Due to the growing importance and utility of the chromenes, different methodologies have been reported for their preparation .…”

Biodiscoveries within the Australian plant genus Eremophila based on international and interdisciplinary collaboration: results and perspectives on outstanding ethical dilemmas

“…Ó 2022 The Authors. (Liu et al, 2016;McNair et al, 2018;Lima et al, 2019;Gimenes et al, 2020;Malik et al, 2020;Nair et al, 2020;Liang et al, 2021). Many of these have shown great potential as drug leads within disease areas covering type 2 diabetes (T2D), infectious diseases (antibacterial and antifungal compounds), malaria and cancer, the main aim being to foster sustainable drug discovery.…”

“…A central part of this research is development and application of new state-of-the-art bioanalytical techniques for advanced chemical and pharmacological profiling of complex extracts. This includes highresolution polypharmacological inhibition profiling (Zhao et al, 2018(Zhao et al, , 2019bLi et al, 2019;Ardalani et al, 2021;Liang et al, 2021) and ligand fishing (Wubshet et al, 2015;Petersen et al, 2019) for identification of bioactive constituents in crude extracts -followed by high-performance, liquid chromatography, photodiode array detection, high-resolution mass spectrometry, solid phase extraction and nuclear magnetic resonance spectroscopy (HPLC-PDA-HRMS-SPE-NMR) analysis for full structural identification of individual constituents (Lima et al, 2017;Zhao et al, 2018). Similarly, bioactivity-correlated metabolomics and bioaffinity NMR are techniques regularly employed to study bioactive natural products (Liu et al, 2017;Broholm et al, 2019).…”

Mass Spectrometry-Based Metabolomics of Phytocannabinoids from Non-Cannabis Plant Origins

“…is distributed and found particularly in alpine grasslands, meadows, and humid grasslands at an altitude above 2500 m [ 57 ]. Its aerial part had been used to isolate chromene meroterpenoids known as (+)−/(−)-rhodonoids and capitachromenic acids [ 58 , 59 , 60 ]. The later had also shown α-glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity [ 59 ].…”

“…Its aerial part had been used to isolate chromene meroterpenoids known as (+)−/(−)-rhodonoids and capitachromenic acids [ 58 , 59 , 60 ]. The later had also shown α-glucosidase and protein-tyrosine phosphatase 1B (PTP1B) inhibitory activity [ 59 ]. The inhibition of PTP1B consequently prolongs the efficiency of insulins in glucose homeostasis.…”