2. Academic Validation
  3. New benzophenone analogs from Nigrospora sphaerica and their inhibitory activity against PD-1/PD-L1 interactions

New benzophenone analogs from Nigrospora sphaerica and their inhibitory activity against PD-1/PD-L1 interactions

  • Bioorg Chem. 2024 Dec:153:107899. doi: 10.1016/j.bioorg.2024.107899.
Qi-Xuan Kuang 1,  Yu-Qing Huang 1,  Yan-Qiu Ruan 2,  Heng-Zhou Lai 1,  Jing Long 1,  Chen-Yi Yan 2,  Hao-Ran Lei 2,  Da-Le Guo 2,  Yun Deng 3,  Feng-Ming You 4,  Yi-Fang Jiang 5
Affiliations

Affiliations

  • 1 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, People's Republic of China.
  • 2 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People's Republic of China.
  • 3 State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, People's Republic of China. Electronic address: dengyun@cdutcm.edu.cn.
  • 4 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, People's Republic of China. Electronic address: youfengming@cdutcm.edu.cn.
  • 5 TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, People's Republic of China. Electronic address: jiangyifang@cdutcm.edu.cn.
PMID: 39454494 DOI: 10.1016/j.bioorg.2024.107899
Abstract

Four newly identified benzophenone analogs [nigrophenone A-D (1-4)] and a pyrrolidinone analog [nigropyrrolidinone (5)], alongside thirteen known congeners (6-18), were isolated from Nigrospora sphaerica. Transcriptome analysis revealed that 6 might have the potential to modulate T-cell immunity. Quantitative measurements of the binding affinities between eighteen natural molecules and the immunological checkpoint receptors PD-1 and PD-L1 were performed using Surface Plasmon Resonance (SPR). The results of SPR analysis showed that 1-18 have KD values ranging from 1.8 to 99.5 μM for PD-1 and from 10.6 to 99.5 μM for PD-L1. Competitive inhibition studies, employing SPR and ELISA assays, have indicated that compounds 6, 10, 15, and 18 are capable of inhibiting the PD-1/PD-L1 interaction. Additionally, compound 6 exhibited notable in vitro Anticancer potency through the augmentation of activating signals and the upregulation of PD-1 expression on CD8+ T cells, concurrently elevating the secretion of IFN-γ and IL-2, thereby inhibiting the proliferation of LLC and MC38 cells and promoting MC38 Apoptosis. Moreover, compound 6 modulates the PI3K/Akt pathway, which is a key downstream effector of the PD-1/PD-L1 axis. These compounds are considered promising candidates for more in-depth exploration because they could significantly inhibit PD-1/PD-L1 interactions in tumor immunotherapy.

Keywords

Benzophenone analogs; Immunotherapy; Nigrospora sphaerica; PD-1/PD-L1; Small-molecule inhibitor.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z