Issue 1, 2023

Synthesis of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones via Ugi–Zhu reaction and in vitro activity assays against human SARS-CoV-2 and in silico studies on its main proteins

Abstract

An Ugi–Zhu three-component reaction (UZ-3CR) coupled in one pot manner to a cascade process (N-acylation/aza Diels–Alder cycloaddition/decarboxylation/dehydration) was performed to synthesize a series of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones in 45 to 82% overall yields using ytterbium triflate as a catalyst, toluene as a solvent, and microwaves as a heat source. The synthesized molecules were evaluated in vitro against human SARS-CoV-2 through a time-of-addition approach, finding that compound 1e, at a concentration of 10.0 μM, exhibited a significant reduction at the initial infection stages, thus showing prophylactic potential. On the other hand, it was found that compound 1d, at the same concentration, was significantly active when applied post-infection, thus exhibiting a therapeutic profile. Moreover, compound 1f showed both, prophylactic and therapeutic activity. Then, to understand interactions between synthesized compounds and the main proteins related to the virus, docking studies were performed on spike-glycoprotein, main-protease, and Nsp3 protein, finding moderate to strong binding energies, matching accurately with the in vitro results. Additionally, a pharmacophore model was computed behind further rational drug design.

Graphical abstract: Synthesis of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones via Ugi–Zhu reaction and in vitro activity assays against human SARS-CoV-2 and in silico studies on its main proteins

Supplementary files

Article information

Article type
Research Article
Submitted
25 Sep 2022
Accepted
11 Nov 2022
First published
18 Nov 2022

RSC Med. Chem., 2023,14, 154-165

Synthesis of bis-furyl-pyrrolo[3,4-b]pyridin-5-ones via Ugi–Zhu reaction and in vitro activity assays against human SARS-CoV-2 and in silico studies on its main proteins

I. Morales-Salazar, F. P. Montes-Enríquez, C. E. Garduño-Albino, M. A. García-Sánchez, I. A. Ibarra, Y. Rojas-Aguirre, M. E. García-Hernández, R. E. Sarmiento-Silva, S. L. Alcaraz-Estrada, E. Díaz-Cervantes, E. González-Zamora and A. Islas-Jácome, RSC Med. Chem., 2023, 14, 154 DOI: 10.1039/D2MD00350C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements