Discovery of Novel Polycyclic Polyprenylated Acylphloroglucinols from the Fruits of As Antitumor Agents by Suppressing the STAT3 Signaling

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Oct 13

PMID 34638708

Citations 1

Authors

Shan Jin

Wen Wang

Fei Gan

Wenli Xie

Jing Xu

Yu Chen

Zhinan Mei

Guangzhong Yang

Affiliations

Soon will be listed here.

Abstract

Pharmacologic studies have revealed that polycyclic polyprenylated acylphloroglucinols (PPAPs) collectively exhibit a broad range of biological activities, including antineoplastic potential. Here, six new PPAPs, named garcixanthochymones F-K (, , , , , and ), together with nine known analogues were isolated from the fruits of . Their structures were elucidated based on the spectroscopic data, including UV, HRESIMS, and NMR, and quantum chemical calculations. All the isolated PPAPs were tested for anti-proliferative activity against four human tumor cell lines, including SGC7901, A549, HepG2, and MCF-7. Most of the PPAPs possessed high anti-proliferative activity with IC values in the range of 0.89 to 36.98 μM, and significant apoptosis was observed in MCF-7 cells exposed to compounds and . Besides, docking results showed that compounds and could strongly combine with the Src homology 2 (SH2) domain of STAT3 via hydrogen bond and hydrophobic interaction, which is one of the key oncogenes and crucial therapeutic targets. Furthermore, compounds and efficiently downregulated the expression of p-STAT3 and pivotal effector proteins involved in oncogenic signaling pathways of MCF-7 cells.

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