# Pyrimidine-containing natural products: occurrences and biological activities **Authors:** Jian-Neng Yao, Yongjie Zhu, He-Ping Chen, Yihua Chen PMC · DOI: 10.1007/s13659-025-00583-y · Natural Products and Bioprospecting · 2026-02-04 ## TL;DR This review explores pyrimidine-containing natural products and their diverse biological activities, aiming to highlight their potential for drug development. ## Contribution The paper provides a comprehensive survey of pyrimidine-containing natural products from 2004 to 2025, emphasizing their structural diversity and therapeutic potential. ## Key findings - 156 pyrimidine-containing compounds were analyzed for their structural and biological features. - These compounds show a wide range of activities, including anticancer, antiviral, and anti-inflammatory effects. - The review highlights the potential of these natural products for lead compound optimization and drug development. ## Abstract Nitrogen-containing core structure pyrimidine has long been regarded as one of the privileged scaffolds for novel drug development. Natural products embedded with pyrimidine motifs are distinguished by their exceptional scaffold diversity and vast structural complexity, which endow them with versatile biological activities, including anticancer, antiviral, antifungal and anti-inflammatory activities. This review is dedicated to surveying a series of structurally distinctive naturally occurring compounds characterized by the presence of an aromatic heterocyclic pyrimidine moiety covering from 2004 to early 2025. Multiple key aspects of these 156 pyrimidine-containing compounds, including natural sources, features of chemical structure, biological activities, as well as biosynthetic studies are summarized. The review emphasizes the enduring potential of natural products, highlighting their inherent capacity for medication and optimization to fuel the pipeline of lead compound targeting major disease and providing new window for overview of these pyrimidine-containing natural products. Overall, this review aims to unlocking the potential of these isolates. It thus offers a fresh reference for the exploitation of pyrimidine-containing natural products, with the ultimate goal of realizing their therapeutic potential. ## Linked entities - **Chemicals:** pyrimidine (PubChem CID 9260) - **Diseases:** cancer (MONDO:0004992) ## Full-text entities - **Genes:** CDK9 (cyclin dependent kinase 9) [NCBI Gene 1025] {aka C-2k, CDC2L4, CTK1, PITALRE, TAK}, ADK (adenosine kinase) [NCBI Gene 132] {aka AK}, RPS6KA3 (ribosomal protein S6 kinase A3) [NCBI Gene 6197] {aka CLS, HU-3, ISPK-1, MAPKAPK1B, MRX19, RSK}, XBP1 (X-box binding protein 1) [NCBI Gene 7494] {aka TREB-5, TREB5, XBP-1, XBP2}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, Btk (Bruton agammaglobulinemia tyrosine kinase) [NCBI Gene 12229] {aka xid}, ACHE (acetylcholinesterase (Yt blood group)) [NCBI Gene 43] {aka ACEE, ARACHE, N-ACHE, YT}, CMTR1 (cap methyltransferase 1) [NCBI Gene 23070] {aka FTSJD2, KIAA0082, MTr1, hMTr1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, PRKACA (protein kinase cAMP-activated catalytic subunit alpha) [NCBI Gene 5566] {aka CAFD1, PKACA, PPNAD4}, GSK3A (glycogen synthase kinase 3 alpha) [NCBI Gene 2931] - **Diseases:** lymphoma (MESH:D008223), cytotoxicity (MESH:D064420), cancer (MESH:D009369), infectious diseases (MESH:D003141), leukemia (MESH:D007938), epidermoid carcinoma (MESH:D002294), multiple myeloma (MESH:D009101), inflammatory (MESH:D007249), central nervous system disorders (MESH:D002493), pulmonary toxicity (MESH:D008171), lymphoblastic leukemia (MESH:D054198), platelet aggregation (MESH:D001791), renal, prostate and CNS tumor (MESH:D011472), cardiovascular diseases (MESH:D002318), influenza (MESH:D007251) - **Chemicals:** jasplakinolide (MESH:C057531), puromycin (MESH:D011691), pyridine (MESH:C023666), doxorubicin (MESH:D004317), sesquiterpene (MESH:D012717), withanolide (MESH:D054358), triterpenoid (MESH:D014315), sulfoxide (MESH:C005746), n-butanol (MESH:D020001), Purine (MESH:C030985), barbituric acid (MESH:C032232), Sangivamycin (MESH:C005699), N6-(4-hydroxybenzyl)-adenine riboside (MESH:C519742), 13C (MESH:C000615229), 3beta-purine-daturmetelide U (-), thymine (MESH:D013941), Sorangiadenosine (MESH:C529592), cytosine (MESH:D003596), Oxetanocin A (MESH:C051061), eudesmane (MESH:C015872), ( +)-agelasine B (MESH:C054174), Arbusculidine A (MESH:C000599863), quinazoline (MESH:D011799), Adenosine (MESH:D000241), D-glucose (MESH:D005947), boningmycin (MESH:C555678), N6-(2-hydroxyethyl)adenosine (MESH:C528186), methanol (MESH:D000432), diterpene (MESH:D004224), sugar (MESH:D000073893), L-leucine (MESH:D007930), machilaminoside B (MESH:C517121), Herbicidins (MESH:C013551), Tubercidin (MESH:D014372), uracil (MESH:D014498), variolin B (MESH:C474921), pyrrolo[2,3-d]pyrimidine (MESH:C450639), cytochalasins (MESH:D003572), oxime (MESH:D010091), polyketide (MESH:D061065), 5'-deoxy-5-iodotubercidin (MESH:C040541), 2-aminopyrimidine (MESH:C012180), imidazole (MESH:C029899), chloroquine (MESH:D002738), Aplidiopsamine A (MESH:C555847), bleomycin (MESH:D001761), beta-caryophyllene (MESH:C024714), amino-nucleoside (MESH:D011692), S-adenosyl-L-methionine (MESH:D012436), albucidin (MESH:C544289), N (MESH:D009584), cucurbitane (MESH:C514277), E-212 (MESH:D014127), verapamil (MESH:D014700), NO (MESH:D009614), adenine (MESH:D000225), Axistatins 1- (MESH:C581273), Ingenine A (MESH:C000606941), alkaloid (MESH:D000470), NC0604 (MESH:C553468) - **Species:** Trypanosoma brucei (species) [taxon 5691], Enterococcus faecalis (species) [taxon 1351], Oreocome striata (species) [taxon 1508160], Millettia laurentii (species) [taxon 2747815], Staphylococcus aureus (species) [taxon 1280], Human immunodeficiency virus (species) [taxon 12721], Porifera (sponges, phylum) [taxon 6040], Pestalotiopsis hainanensis (species) [taxon 679339], Human immunodeficiency virus 1 (no rank) [taxon 11676], Chalara sp. (species) [taxon 36534], Withania somnifera (ashwagandha, species) [taxon 126910], Herdmania momus (red throated ascidian, species) [taxon 7733], Sorangium cellulosum (species) [taxon 56], Cucurbita pepo (species) [taxon 3663], Zingiber officinale (ginger, species) [taxon 94328], Agelas axifera (species) [taxon 332232], Lasiodiplodia sp. (species) [taxon 1891967], Lactuca tatarica (species) [taxon 75952], Streptomyces tubercidicus (species) [taxon 47759], Streptomyces rimosus (species) [taxon 1927], Cryptococcus neoformans (Cryptococcus neoformans serotype A, species) [taxon 5207], Peganum harmala (species) [taxon 43879], Annona foetida (species) [taxon 1937578], Selaginella delicatula (species) [taxon 1353961], Rhodomela confervoides (species) [taxon 35163], Streptomyces fungicidicus (species) [taxon 68203], Coridius chinensis (species) [taxon 1028097], Streptomyces toyocaensis (species) [taxon 55952], Datura stramonium (common thornapple, species) [taxon 4076], Stylissa carteri (species) [taxon 279588], Gastrodia elata (species) [taxon 91201], Sphaeranthus indicus (species) [taxon 1205786], Trypoxylus dichotomus (species) [taxon 273928], Cordyceps militaris (species) [taxon 73501], Homo sapiens (human, species) [taxon 9606], Magallana rivularis (species) [taxon 37644], Streptomyces vendargensis (species) [taxon 67374], Mycosarcoma maydis (corn smut, species) [taxon 5270], Mus musculus (house mouse, species) [taxon 10090], Plasmodium falciparum (malaria parasite P. falciparum, species) [taxon 5833], Diplosoma (genus) [taxon 216023], Streptomyces sp. (species) [taxon 1931], Escherichia coli (E. coli, species) [taxon 562], Acanthostrongylophora ingens (species) [taxon 237153], Agelas nakamurai (species) [taxon 279581], Ophiocordyceps sinensis (species) [taxon 72228], Leishmania donovani (species) [taxon 5661], Paenibacillus kribbensis (species) [taxon 172713] - **Mutations:** A3 adenosine, Serine/Threonine - **Cell lines:** MCF-7 — Homo sapiens (Human), Invasive breast carcinoma of no special type, Cancer cell line (CVCL_0031), PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481), HL-60 — Homo sapiens (Human), Adult acute myeloid leukemia with maturation, Cancer cell line (CVCL_0002), HEK-293 — Homo sapiens (Human), Transformed cell line (CVCL_0045), A549 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_0023), HCT-116 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_0291), Dd2 — Cricetulus griseus (Chinese hamster), Transformed cell line (CVCL_YD16), U937 — Homo sapiens (Human), Adult acute monocytic leukemia, Cancer cell line (CVCL_0007), 3D7 — Mus musculus (Mouse), Hybridoma (CVCL_KS87), HST116 — Homo sapiens (Human), Tongue squamous cell carcinoma, Cancer cell line (CVCL_E316), K562 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0004), NK84-0218 — Homo sapiens (Human), Transformed cell line (CVCL_8V29), HFF — Homo sapiens (Human), Finite cell line (CVCL_3285), L5178Y — Mus musculus (Mouse), Mouse thymic lymphoma, Cancer cell line (CVCL_2097), RAW264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), KB — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0372), Hela — Homo sapiens (Human), Human papillomavirus-related endocervical adenocarcinoma, Cancer cell line (CVCL_0030), BCG-813 — Homo sapiens (Human), Finite cell line (CVCL_2H04), PC9 — Homo sapiens (Human), Lung adenocarcinoma, Cancer cell line (CVCL_B260), K562/A02 — Homo sapiens (Human), Blast phase chronic myelogenous leukemia, BCR-ABL1 positive, Cancer cell line (CVCL_0368), HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), BV2 — Mus musculus (Mouse), Transformed cell line (CVCL_0182), Jurkat — Homo sapiens (Human), Childhood T acute lymphoblastic leukemia, Cancer cell line (CVCL_0065), L1210 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0382) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12868415/full.md ## Figures 19 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12868415/full.md ## References 6 references — full list in the complete paper: https://tomesphere.com/paper/PMC12868415/full.md --- Source: https://tomesphere.com/paper/PMC12868415