Curcumin for gastric cancer:Mechanism prediction via network pharmacology,docking,and in vitro experiments

BACKGROUND Curcumin originates from the natural herb turmeric,and its antitumor effects have been known about for a long time.However,the mechanism by which curcumin affects gastric cancer(GC)has not been elucidated.AIM To elucidate the potential mechanisms of curcumin in the treatment of GC.METHODS Network pharmacological approaches were used to perform network analysis of Curcumin.We first analyzed Lipinski’s Rule of Five for the use of Curcumin.Curcumin latent targets were predicted using the PharmMapper,SwissTargetPrediction and DrugBank network databases.GC disease targets were mined through the GeneCard,OMIM,DrugBank and TTD network databases.Then,GO enrichment,KEGG enrichment,protein-protein interaction(PPI),and overall survival analyses were performed.The results were further verified through molecular docking,differential expression analysis and cell experiments.RESULTS We identified a total of 48 curcumin-related genes with 31 overlapping GC-related targets.The intersection targets between curcumin and GC have been enriched in 81 GO biological processes and 22 significant pathways.Following PPI analysis,6 hub targets were identified,namely,estrogen receptor 1(ESR1),epidermal growth factor receptor(EGFR),cytochrome P450 family 3 subfamily A member 4(CYP3A4),mitogen-activated protein kinase 14(MAPK-14),cytochrome P450 family 1 subfamily A member 2(CYP1A2),and cytochrome p450 family 2 subfamily B member 6(CYP2B6).These factors are correlated with decreased survival rates among patients diagnosed with GC.Molecular docking analysis further substantiated the strong binding interactions between Curcumin and the hub target genes.The experimental findings demonstrated that curcumin not only effectively inhibits the growth of BGC-823 cells but also suppresses their proliferation.mRNA levels of hub targets CYP3A4,MAPK14,CYP1A2,and CYP2B6 in BGC-823 cells were significantly increased in each dose group.CONCLUSION Curcumin can play an anti-GC role through a variety of targets,pathways and biological processes.

A Simple Building Block with Noncovalently Conformational Locks towards Constructing Low-Cost and High-Performance Nonfused Ring Electron Acceptors

Nonfused ring electron acceptors(NFREAs)have attracted much attention due to their concise synthetic routes and low cost.However,developing high-performance NFREAs with simple structure remains a great challenge.In this work,a simple building block(POBT)with noncovalently conformational locks(No CLs)was designed and synthesized.Single-crystal X-ray study indicated the presence of S…O NOCLs in POBT,thus enabling it to possess a coplanar conformation comparable to that of fused-ring CPT.Two novel NFREAs based on CPT and POBT were developed,namely TT-CPT and TT-POBT,respectively.Besides,TT-POBT possessed a smaller Stokes shift and a reduced reorganization energy compared with TT-CPT,indicating the introduction of S…O No CLs can enhance the molecular rigidity even if simplifying the molecular structure.As a result,the TT-POBT-based PSC device afforded an impressive power conversion efficiency of 11.15%,much higher than that of TT-CPT counterpart(7.03%),mainly resulting from the tighterπ-πstacking,improved and balanced charge transport,and more favorable film morphology.This work demonstrates the potential of the simple building block POBT with No CLs towards constructing low-cost and highperformance NFREAs.