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A rationally designed family of NSAID-derived alkyne ligands was coordinated to JohnPhos−gold(I) fragments, yielding eight new alkynyl gold(I) derivatives. Naproxen, ibuprofen, and salicylic-acid based complexes showed potent antiproliferative activity in Caco-2/TC7 colon cells, outperforming oxaliplatin and matching auranofin, with reduced cytotoxicity in breast cancer lines and nonmalignant cells. Mechanistically, the lead complex [Au(L1)JP] (1) inhibited thioredoxin reductase, induced ROS overproduction, disrupted mitochondrial membrane potential, and caused G1 arrest with only marginal apoptosis, suggesting additional cell-death or cytostatic effects. It also selectively inhibited COX-2 over COX-1 and reduced IL-8 expression via posttranscriptional anti-inflammatory action. These findings support multitarget NSAID-derived alkynyl gold(I) agents for CRC intervention by combining COX-2 modulation with cellular disruption.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/dual-action-nsaid-goldi-alkynyl-hybrids-for-synergistic-antiinflammatory-and-anticancer-therapy-of-colorectal-cancer/353997/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/dual-action-nsaid-goldi-alkynyl-hybrids-for-synergistic-antiinflammatory-and-anticancer-therapy-of-colorectal-cancer/353997.png","ImageObject",300,407,{"name":92,"@type":93},"Aria Callaghan","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-27","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",16,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What is the main therapeutic rationale behind the NSAID-derived alkynyl gold(I) hybrids for colorectal cancer?","Question",{"text":113,"@type":114},"The study targets chronic inflammation and redox dysregulation by combining disruption of cellular redox systems with selective COX-2 modulation, aiming for synergistic anti-inflammatory and anticancer effects.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which experimental complex showed the strongest biological activity, and what key mechanisms does it trigger?",{"text":118,"@type":114},"Complex [Au(L1)JP] (1) was the most active. It inhibits thioredoxin reductase, increases ROS, disrupts mitochondrial membrane potential, and induces G1-phase arrest with only marginal apoptosis.",{"name":120,"@type":111,"acceptedAnswer":121},"How do the complexes affect anti-inflammatory signaling compared with COX-1 and COX-2?",{"text":122,"@type":114},"The most active complex selectively inhibits COX-2 over COX-1 and reduces IL-8 expression without affecting PTGS2 transcription, indicating a posttranscriptional anti-inflammatory action.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},353997,1790172844,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":140,"language":141,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":142,"faqs":143,"seo_title":144,"seo_description":67,"update_tm":145,"read_time":146},962084926284,"https://ap-avatar.wpscdn.com/davatar_29158cc5080c5b710cf443261637dec0","This article is licensed under CC-BY 4.0   \n[pubs.acs.org/IC](pubs.acs.org/IC)  Article   \nDual-Action NSAID-Gold(I) Alkynyl Hybrids for Synergistic AntiInflammatory and Anticancer Therapy of Colorectal Cancer  \nJavier Sáez, Luis Vicente Herrera-Marcos, María Jeśus Rodríguez-Yoldi, M. Concepción Gimeno, * and Elena Cerrada *  \n Cite This: Inorg. Chem. 2026, 65, 7210−7223  \nRead Online  \n\n|  |  |  |  |  |  |\n| --- | --- | --- | --- | --- | --- |\n| ACCESS   | Metrics & More |  |  Article Recommendations |  | *sı Supporting Information |\n\nABSTRACT: Colorectal cancer (CRC) remains a major global health challenge, in which chronic inflammation and redox dysregulation are key drivers of tumor progression. Here, we report a rationally designed family of NSAID-derived alkyne ligands coordinated to JohnPhos−gold(I) fragments, affording eight new alkynyl gold(I) derivatives. Complexes based on naproxen, ibuprofen, and salicylic acid derivatives display potent antiproliferative activity against Caco-2/TC7 colon cancer cells, outperforming oxaliplatin and being comparable to auranofin, while showing markedly reduced cytotoxicity in breast cancer lines and nonmalignant cells, thus indicating promising selectivity. Mechanistic studies revealed that the most active complex, [Au(L1)JP] ( 1), which contains a naproxenderived alkyne, inhibits thioredoxin reductase (TrxR), triggers ROS overproduction, disrupts mitochondrial membrane potential, and induces G1-phase arrest while only marginally increasing apoptosis. This suggests the involvement of additional forms of cell death or cytostatic effects. Additionally, complex 1 selectively inhibits the enzyme cyclooxygenase-2 (COX-2) over COX-1 and reduces IL-8 expression without affecting PTGS2 transcription, highlighting a posttranscriptional anti-inflammatory action. These results support NSAID-derived alkynyl gold(I) complexes as promising multitarget agents for colorectal cancer intervention, combining disruption and COX-2 modulation.  \n1. INTRODUCTION  \nColorectal cancer (CRC), a disease characterized by abnormal cell growth in the colon and rectum, ranks among the leading causes of cancer-related morbidity and mortality worldwide, significantly contributing to global health burdens. Despite advances in screening and treatment, the development of CRC remains driven by complex interactions among genetic, environmental, and lifestyle factors. Most CRC cases have been associated with environmental factors rather than heritable genetic changes. Risk factors include food-borne and ecological mutagens, specific intestinal microbes and pathogens, and chronic intestinal inflammation, which often precedes tumor development.1 These events cause structural changes in DNA, transforming normal cells into cancer cells.2 In recent years, inflammation has become a key factor in the development and progression of colorectal cancer. Chronic inflammation, especially within the colonic microenvironment, has been associated with promoting neoplastic transformation through mechanisms such as cellular damage, genomic instability, and the activation of oncogenic pathways.3 Tumor progression relies on the interactions between tumor cells and components of the tumor microenvironment. Cells in the microenvironment release pro-inflammatory cytokines, chemokines, growth factors, and proteases that regulate the growth, differentiation, and survival of cancer cells, thereby facilitating angiogenesis and metastasis.4 Although chronic inflammation  \n© 2026 The Authors. Published by American Chemical Society  \nmay be involved in all three stages of tumor development (initiation, promotion, and progression) it appears to play a  \nsignificant role in tumor promotion and progression.5  \nInflammatory conditions such as inflammatory bowel disease (IBD), which includes Crohn’s disease and ulcerative colitis, are well-recognized risk factors for colorectal cancer, emphasizing the connection between chronic inflammation and tumorigene","cbCaiiwpWvKhaEzQ","https://ap.wps.com/l/cbCaiiwpWvKhaEzQ","pdf",6879805,14,"English","# Abstract\n# Introduction","[{\"question\":\"What is the main therapeutic rationale behind the NSAID-derived alkynyl gold(I) hybrids for colorectal cancer?\",\"answer\":\"The study targets chronic inflammation and redox dysregulation by combining disruption of cellular redox systems with selective COX-2 modulation, aiming for synergistic anti-inflammatory and anticancer effects.\"},{\"question\":\"Which experimental complex showed the strongest biological activity, and what key mechanisms does it trigger?\",\"answer\":\"Complex [Au(L1)JP] (1) was the most active. It inhibits thioredoxin reductase, increases ROS, disrupts mitochondrial membrane potential, and induces G1-phase arrest with only marginal apoptosis.\"},{\"question\":\"How do the complexes affect anti-inflammatory signaling compared with COX-1 and COX-2?\",\"answer\":\"The most active complex selectively inhibits COX-2 over COX-1 and reduces IL-8 expression without affecting PTGS2 transcription, indicating a posttranscriptional anti-inflammatory action.\"}]","Dual-Action NSAID-Gold(I) Alkynyl Hybrids for Synergistic AntiInflammatory and Anticancer Therapy of Colorectal Cancer | PDF",1790108405,35]