{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:46:53Z","timestamp":1792180013193,"version":"4.4.0"},"reference-count":138,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cDun\u0103rea de Jos University of Gala\u021bi\u201d","award":["7969\/31 March 2025"],"award-info":[{"award-number":["7969\/31 March 2025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cancer is a leading cause of death globally, claiming millions of lives each year. Despite the availability of numerous anticancer drugs, the need for new treatment options remains essential. Many current therapies come with significant toxicity, lead to various side effects, or do not consistently deliver the expected therapeutic results. Purines and pyrimidines are fundamental building blocks of nucleic acids and play crucial roles in cellular metabolism and signaling. Recent advances in medicinal chemistry have led to the development and synthesis of various derivatives that exhibit selective cytotoxic effects against cancer cells while minimizing toxicity to healthy tissues. Purine and pyrimidine scaffolds, due to their well-established biological roles and structural versatility, have emerged as key pharmacophoric fragments in anticancer drug discovery. In recent years, the rational design of hybrid molecules incorporating these heterocycles has shown promise in overcoming drug resistance, improving target selectivity, and enhancing pharmacological profiles. Purine and pyrimidines scaffolds hold significant potential as foundations for novel antitumor drugs, with established representatives in cancer treatment, including 5-fluorouracil, cladribine, capecitabine, and several others. In addition, the article discusses the challenges and future developments of purine and pyrimidine derivatives and hybrid molecules as antitumor drugs and emphasizes the need for continued research to optimize their effectiveness and reduce side effects. Overall, the innovative use of these compounds represents a major advance in targeted cancer therapy and holds promise for improving the therapeutic efficacy of malignant diseases.<\/jats:p>","DOI":"10.3390\/molecules30132707","type":"journal-article","created":{"date-parts":[[2025,6,24]],"date-time":"2025-06-24T04:37:21Z","timestamp":1750739841000},"page":"2707","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Hybrid Molecules with Purine and Pyrimidine Derivatives for Antitumor Therapy: News, Perspectives, and Future Directions"],"prefix":"10.3390","volume":"30","author":[{"given":"Simona","family":"Iacob (Ciobotaru)","sequence":"first","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia-Simona","family":"Stefan","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurel","family":"Nechita","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madalina-Nicoleta","family":"Matei","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-9731","authenticated-orcid":false,"given":"Elena-Lacramioara","family":"Lisa","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Tutunaru","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iuliu","family":"Fulga","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Fulga","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9985-5057","authenticated-orcid":false,"given":"Alina-Georgiana","family":"Cristea (Hohota)","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oana-Maria","family":"Dragostin","sequence":"additional","affiliation":[{"name":"Research Centre in the Medical-Pharmaceutical Field, Faculty of Medicine and Pharmacy, \u201cDunarea de Jos\u201d University of Galati, 35 AL Cuza St., 800010 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. 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