# Nature-Inspired Gold(I) Complexes as Anticancer Agents: Ligand Design, Structure–Activity Relationships, and Mechanisms **Authors:** Amrin Begum, Navya PN, Pooran Kumar, Srinivasa Reddy Telukutla, Ruchika Ojha, Magdalena Plebanski, Suresh K. Bhargava PMC · DOI: 10.3390/cancers18040631 · 2026-02-15 ## TL;DR This review explores how nature-inspired gold(I) complexes can be designed to improve their anticancer activity and effectiveness compared to traditional drugs. ## Contribution The paper provides a structure–activity perspective on nature-inspired gold(I) complexes for anticancer drug design. ## Key findings - Nature-inspired ligands enhance the activity and stability of gold(I) complexes. - Heterobimetallic gold complexes show synergistic therapeutic effects. - Gold(I) complexes target enzymes like thioredoxin reductase in cancer cells. ## Abstract Gold complexes have emerged as promising anticancer agents due to their unique chemical properties and alternative mechanisms of action compared to traditional chemotherapy drugs. Their significance lies in their potential to overcome drug resistance and target cancer cells more selectively by targeting enzymes such as thioredoxin reductase, which is overexpressed in several cancer cells. In drug discovery, nature-inspired ligands provide structurally diverse and biologically relevant frameworks that enhance the activity and stability of gold complexes. Recent studies increasingly focus on gold(I) complexes derived from these ligands. In addition, heterobimetallic gold complexes have attracted attention for their synergistic therapeutic effects. Together, these systems represent an important direction in anticancer drug design. Nature-inspired ligands, including natural product scaffolds and bio-inspired motifs, have emerged as an important source for the development of gold(I) complexes with promising preclinical anticancer activity. This review focuses on structurally characterised gold(I) complexes derived from these ligands, emphasising how ligand structure and gold coordination influence the biological activity. This paper covers the synthesis of nature-inspired gold(I) complexes, alkynyl, N-heterocyclic carbene (NHC), heteroatom-donor, and heterobimetallic complexes, which collectively contribute to enhanced cytotoxicity, stability, and mechanistic diversity. By focusing on these nature-inspired gold(I) complexes, this review provides a concise structure–activity perspective and outlines future opportunities for rational design in anticancer research. ## Linked entities - **Chemicals:** gold (PubChem CID 23985), N-heterocyclic carbene (PubChem CID 2801129) - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** ABCB1 (ATP binding cassette subfamily B member 1) [NCBI Gene 5243] {aka ABC20, CD243, CLCS, ENPAT, GP170, MDR1}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, HMGN4 (high mobility group nucleosomal binding domain 4) [NCBI Gene 10473] {aka HMG17L3, NHC}, PRDX5 (peroxiredoxin 5) [NCBI Gene 25824] {aka ACR1, AOEB166, B166, HEL-S-55, PLP, PMP20}, MMP2 (matrix metallopeptidase 2) [NCBI Gene 4313] {aka CLG4, CLG4A, MMP-2, MMP-II, MONA, TBE-1}, GSR (glutathione-disulfide reductase) [NCBI Gene 2936] {aka CNSHA10, GR, GSRD, HEL-75, HEL-S-122m} - **Diseases:** hepatocellular carcinoma (MESH:D006528), bladder cancer (MESH:D001749), breast adenocarcinoma (MESH:D001943), estrogen (MESH:D056828), ovarian cancer (MESH:D010051), T-cell lymphoblastic leukaemia (MESH:D015458), oedema (MESH:C536897), cytotoxic (MESH:D064420), metastasis (MESH:D009362), colon cancer (MESH:D015179), neuroblastoma (MESH:D009447), renal cancer (MESH:D007680), colon adenocarcinoma, grade II (MESH:D003110), gastric cancer (MESH:D013274), cancer of the uterus (MESH:D014594), Cancer (MESH:D009369), diabetic (MESH:D003920), insomnia (MESH:D007319), lung cancer (MESH:D008175), Alzheimer (MESH:D000544), ND (MESH:C537849), CAM (MESH:D020786), prostate cancer (MESH:D011471), melanoma (MESH:D008545), inflammatory (MESH:D007249), injury to (MESH:D014947), mitochondrial dysfunction (MESH:D028361), pancreatic ductular adenocarcinoma (MESH:D010190), cervical cancer (MESH:D002583) - **Chemicals:** heterocyclic compound (MESH:D006571), hydrogen (MESH:D006859), fumitremorgin C (MESH:C010522), camptothecin (MESH:D002166), verapamil HCl (MESH:D014700), p-cymene (MESH:C007210), oxadiazole (MESH:D010069), ROS (MESH:D017382), selenocysteine (MESH:D017279), vasicine (MESH:C019592), DAPI (MESH:C007293), methanethiol (MESH:C005231), Pyrimidines (MESH:D011743), phosphine (MESH:C044646), Quinoline (MESH:C037219), I (MESH:D007455), taxanes (MESH:D043823), cysteine (MESH:D003545), Quinazoline (MESH:D011799), phosphines (MESH:D010720), quisqualic acid (MESH:D016318), Amino Acid (MESH:D000596), phidianidine B (MESH:C559225), p-toluenethiol (MESH:C540257), titanium (MESH:D014025), thiol (MESH:D013438), selenium (MESH:D012643), vinca alkaloids (MESH:D014748), NHCs (MESH:C010737), echinopsine (MESH:C007574), amine (MESH:D000588), cinchona alkaloids (MESH:D002930), Combretastatin (MESH:C040105), sulphur (MESH:D013455), 1,2,4-oxadiazole (-), cisplatin (MESH:D002945), Ru (MESH:D012428), CA-4 (MESH:C058728), pyridine (MESH:C023666), carbene (MESH:C030011), copper (MESH:D003300), alkaloids (MESH:D000470), silver (MESH:D012834), resveratrol (MESH:D000077185), tegafur (MESH:D005641), dipeptide (MESH:D004151), Pyrimidine (MESH:C030986), phidianidine A (MESH:C559224), imidazole (MESH:C029899), 5-FU (MESH:D005472), Fe (MESH:D007501), auranofin (MESH:D001310), podophyllotoxin (MESH:D011034), Nitrogen (MESH:D009584), paclitaxel (MESH:D017239), histidine (MESH:D006639), ferrocene (MESH:C004998), pterostilbene (MESH:C107773), Stilbene (MESH:D013267), Au (MESH:D006046) - **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090] - **Cell lines:** HT-29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), GXF 251 — Homo sapiens (Human), Gastric carcinoma, Cancer cell line (CVCL_D243), CCRF-CEM — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0207), T24 — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_0554), NIE-115 — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_0451), SKOV-3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532), LXFA 629 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_D189), foreskin fibroblasts — Homo sapiens (Human), Finite cell line (CVCL_VS58), KB-V1 — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_2089), L1210 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0382), Panc-1 — Homo sapiens (Human), Pancreatic ductal adenocarcinoma, Cancer cell line (CVCL_0480), HeLa — Homo sapiens (Human), Human papillomavirus-related cervical squamous cell carcinoma, Cancer cell line (CVCL_T292), OVXF 899 — Homo sapiens (Human), Ovarian adenocarcinoma, Cancer cell line (CVCL_D170), Hep3b — Anopheles gambiae (African malaria mosquito), Spontaneously immortalized cell line (CVCL_Z623), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), MDA-MB 231 — Homo sapiens (Human), Breast adenocarcinoma, Cancer cell line (CVCL_0062), MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), 518A2 — Homo sapiens (Human), Melanoma, Cancer cell line (CVCL_UM77), Hep3B — Homo sapiens (Human), Childhood hepatocellular carcinoma, Cancer cell line (CVCL_0326), MCF — Homo sapiens (Human), Transformed cell line (CVCL_E778), HF — Homo sapiens (Human), Diffuse large B-cell lymphoma germinal center B-cell type, Cancer cell line (CVCL_UI84), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), L929 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_AR58), 5637 — Homo sapiens (Human), Bladder carcinoma, Cancer cell line (CVCL_0126), C-1300 — Mus musculus (Mouse), Mouse neuroblastoma, Cancer cell line (CVCL_4343), 22RV1 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_1045), MAXF 401 — Homo sapiens (Human), Breast carcinoma, Cancer cell line (CVCL_D131), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), UXF 1138 — Homo sapiens (Human), Finite cell line (CVCL_V798), CH1 — Homo sapiens (Human), Transformed cell line (CVCL_N170) ## Figures 8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12940058/full.md --- Source: https://tomesphere.com/paper/PMC12940058