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Planta Med 2025; 91(04): 197-207
DOI: 10.1055/a-2515-9491
Original Papers

Roseoglobuloside A, a Novel Nonanolide, and Identification of Specialized Metabolites as hPTP1B1 – 400 Inhibitors from Mangrove-Dwelling Aspergillus spp

Carlos A. Fajardo-Hernández
1   Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Mexico City, Mexico
,
Ángeles G. Zavala-Sierra
1   Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Mexico City, Mexico
,
Verenice I. Merlin-Lucas
1   Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Mexico City, Mexico
,
Jesús I. Morales-Jiménez
2   Departamento El Hombre y su Ambiente, Universidad Autónoma Metropolitana, Mexico City, Mexico
,
José Rivera-Chávez
1   Instituto de Química, Departamento de Productos Naturales, Universidad Nacional Autónoma de México, Mexico City, Mexico
› InstitutsangabenThis research received financial support by grants from CONACyT/CONAHCyT through project Programa Ciencia de Frontera (CF-2019 – 263 977). It also received partial support from the Dirección General de Asuntos del Personal Académico (DGAPA), Universidad Nacional Autónoma de México (UNAM), through the program Apoyo a Proyectos de Investigación e Innovación Tecnológica (PAPIIT: IN224424). We would like to express our gratitude to those who aided and guided us in the collection of spectroscopic and spectrometric data: Dr. Adriana Romo-Pérez, Dr. María del Carmen García-González, MSc. Elizabeth Huerta (Instituto de Química, UNAM), Dr. Beatriz Quiroz-García (LURMN, IQ-UNAM), and MSc. Maricruz López López for the handling and disposal of hazardous biological infectious waste material. Furthermore, we extend our gratitude to MSc. Everardo Tapia (LANCIC, IQ-UNAM) for his instrumental role in acquiring the MS2 spectra. J. R.-C. is in debt to the Dirección General de Cómputo y de Tecnologías de Información y Comunicación (DGTIC), UNAM, for providing the resources to carry out computational calculations in the Miztli System through the project LANCAD-UNAM-DGTIC-374. This research made use of the resources of the UNAM NMR Laboratory (LURMN) at IQ-UNAM funded by CONAHCyT-Mexico (Project: 0 224 747), and UNAM. C. A. F.-H. and J. R.-C. extend their sincerest gratitude to the undergraduate students Alejandro Jacinto-Olguin, Isela Romero-Bazán, and Itzel Rojas-Zepeda for their invaluable assistance during their laboratory training. C. A. F.-H. is most grateful to CONACyT/CONAHCyT/SECITHI for a postdoctoral fellowship (CVU 739 587) through the program Estancias Posdoctorales por México 2022 (3).
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Abstract

An approach combining enzymatic inhibition and untargeted metabolomics through molecular networking was employed to search for human recombinant full-length protein tyrosine phosphatase 1B (hPTP1 B1 – 400) inhibitors from a collection of 66 mangrove-associated fungal taxa. This strategy prioritized two Aspergillus strains (IQ-1612, section Circumdati, and IQ-1620, section Nigri) for further studies. Chemical investigation of strain IQ-1612 resulted in the isolation of a new nonanolide derivative, roseoglobuloside A (1), along with two known metabolites (2 and 3), whereas strain IQ-1620 led to the isolation of four known naphtho-γ-pyrones and one known diketopiperazine (4–8). Of all isolates, compounds 2, 3, and 7 showed a marked inhibitory effect on hPTP1B1 – 400 with an IC50 value < 20 µM, while 6 showed moderate inhibition with IC50 of 65 µM. Compounds 1 and 8 were inactive at a concentration of 100 µM, whereas 4 and 5 demonstrated significant inhibition at 20 µM. The structure of 1 was established by comprehensive spectroscopic analysis, and its relative and absolute configuration was assigned based on NOE correlations and by comparison of calculated and experimental ECD curves. Molecular docking indicated that these molecules primarily bind to two different allosteric sites, thereby inducing conformational changes that impact enzymatic activity.

Keywords

Aspergillus - Aspergillaceae - nonanolide - hPTP1B1 – 400 - molecular networking - insulin regulation pathway

Supporting Information

    Information about taxa identification, samples collected for isolating fungal organisms, preliminary identification of associated molecules during MN analysis, and spectrometric and spectroscopic data of compounds are available as Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 14. August 2024

Angenommen nach Revision: 10. Januar 2025

Artikel online veröffentlicht:
27. Januar 2025

© 2025. Thieme. All rights reserved.

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