Quinazoline derivatives, a class of nitrogen-containing heterocyclic compounds, have become one of the most intensively studied scaffolds in anticancer drug discovery, and a new hybrid review now offers the first bibliometric map of that research landscape. Published in Discover Chemistry, the study combines a statistical analysis of global publication trends with a pharmacological evaluation of quinazoline-based anticancer compounds, covering the scientific literature from 1992 to 2024. The authors, Fatemeh Azmian Moghadam, Masoud Mokhtary and Seyed Ali Hozni, report that the field has grown steadily over three decades, peaked in 2018, and is now dominated by research groups in Asia and North Africa, with molecular docking and IC50 measurements emerging as the most recent thematic shifts.
To build the dataset, the team searched the Scopus database in June 2024 using a query combining the terms synthesis, anticancer and quinazoline, restricted to ten subject areas including pharmacology, chemistry, biochemistry, chemical engineering and medicine. The initial search returned 591 articles. After duplicates were removed with Scopus’s built-in tools and manual verification, and after screening against inclusion criteria focused on English-language articles directly related to synthesis and anticancer activity, 423 publications remained for analysis. Conference papers were included only if peer-reviewed, and non-final publications were excluded. The authors analyzed the corpus with VOSviewer, chosen for its network visualization capabilities, and with the Biblioshiny package running on the R platform, applying keyword co-occurrence thresholds and Louvain clustering to map intellectual structure.
The publication trend tells a story of gradual maturation followed by rapid expansion. From 1992 to 2014, output rose with a gentle slope, then accelerated sharply to a peak of 45 articles in 2018. Although 2019 brought a steep drop in article counts, the overall trajectory remained upward through the end of the study window. Citation behavior followed a parallel course: the average number of citations per article has increased over the last decade, which the authors interpret as a sign of topical maturity. They caution, however, that citation counts were not normalized for publication year, so older papers had more time to accumulate citations, a limitation that shapes how the citation rankings should be read.
Geographically, the analysis reveals a striking concentration of scientific production. China leads with 887 articles, followed by India with 480 and Egypt with 370, and these three countries also rank first in citations. The authors attribute this Asian and North African dominance to factors including high cancer burden, government funding priorities and pharmaceutical industry growth in regions such as China and India. International collaboration patterns add further texture: the strongest bilateral ties appear between Egypt and Saudi Arabia, Saudi Arabia shows the highest level of single-country publication, and the collaboration network links China with Middle Eastern countries, Egypt and North America. At the institutional level, Al-Azhar University in Egypt tops the ranking with 104 articles, ahead of Shenyang Pharmaceutical University with 87 and King Saud University with 65.
Individual researchers and journals leave their own signatures on the field. The author ZHANG Y leads with 16 articles and the highest citation count, a combination the authors read as both prolific output and acceptable quality. Co-authorship network analysis, restricted to authors with at least three articles and five citations, identified 21 authors organized into four clusters, with researchers in the same cluster working on common topics. Among journals, the European Journal of Medicinal Chemistry published the most articles on the topic, 44, and gathered the most citations, 1,826, followed by Bioorganic and Medicinal Chemistry Letters and Bioorganic Chemistry. Keyword analysis of the corpus, which contained 6,883 author and index keywords in total, distilled 33 index keywords into three thematic clusters and traced their historical evolution, revealing that molecular docking and IC50 are the newest trends alongside established concepts such as synthesis and kinase inhibitors.
Beyond the statistics, the review integrates a pharmacological synthesis of what quinazoline compounds actually do. The scaffold’s therapeutic relevance rests on diverse mechanisms of action, including kinase inhibition, induction of apoptosis and cell cycle arrest. Thematic mapping identified synthesis, anticancer, derivatives, kinase and inhibitors as prominent motor themes, and thematic evolution diagrams show that synthesis- and kinase-related themes have grown in number and weight over the studied period. The most highly cited articles in the corpus describe quinazoline-artemisinin hybrids synthesized under microwave conditions, quinolines and anilinoquinazolines used as carriers for alkylating agents, nanoquinazolines investigated for their potential to increase the effectiveness of cancer immunotherapy, and new VEGFR-2, EGFR and c-Met inhibitors designed to induce apoptosis and arrest cells in the G2/M phase.
The clinical anchor of the field is the family of FDA-approved quinazoline EGFR inhibitors. Drugs such as erlotinib and gefitinib effectively target mutations in non-small cell lung cancer and have improved survival in genetically selected patients, and recent studies highlight their synergy with immunotherapies. The review also surveys newer preclinical directions: quinazoline sulfonamides acting as dual EGFR/VEGFR-2 inhibitors with radiosensitizing potential in vitro and in vivo, quinazoline PI3K inhibitors that suppress the PI3K/Akt/mTOR pathway, and broad-spectrum activity against diverse cell lines, including nanomolar IC50 values against MGC-803 gastric cancer cells. Specific structure-activity signals recur throughout: trifluoromethyl-substituted quinazolines show antiproliferative effects with IC50 values below 3.02 micromolar against prostate cancer cells, and 1,2,3-triazole hybrids enhance MET inhibition with an IC50 of 6.1 micromolar, underscoring the positional importance of triazole substitution.
On the synthetic side, the review catalogs the main routes to the quinazoline core. Classical preparation typically involves constructing the pyrimidine ring through cyclization of anthranilic acid derivatives or functionalizing pre-formed quinazoline cores, with the Niementowski reaction yielding 4(3H)-quinazolinones from anthranilic acids and amides, and amidine or urea intermediates providing access to 2-substituted quinazolines. More recent protocols emphasize greener and faster chemistry, including microwave-assisted synthesis and metal-catalyzed cross-coupling reactions, which reduce reaction times, raise yields and improve functional group tolerance compared with conventional thermal methods. The SAR analysis identifies electron-withdrawing groups at the 6- and 7-positions of the ring as enhancers of kinase inhibition through stronger interactions in the ATP-binding pocket, the 4-anilino substituent as a hallmark of potent EGFR inhibitors, and halogen or trifluoromethyl substitutions as levers that tune electronic distribution, lipophilicity, target binding and cellular uptake.
The authors are explicit about the limits of their analysis. Restricting the search to Scopus may have missed relevant entries indexed in PubMed or Embase, and the absence of citation normalization for publication year favors older, more established works. They also note that translating promising preclinical quinazoline findings into clinical practice faces substantial obstacles, including poor aqueous solubility, limited oral bioavailability and the emergence of drug resistance. Their proposed responses are concrete: novel drug delivery systems such as nanoparticles and liposomes to improve pharmacokinetic profiles, multi-target inhibitors capable of blocking several oncogenic pathways simultaneously to combat resistance, and the application of artificial intelligence and machine learning to accelerate the identification of derivatives with improved potency and selectivity. The conclusion stresses that more rigorous clinical validation is needed to bridge the gap between preclinical findings and clinical practice.
The broader context gives the bibliometric numbers their weight. The World Health Organization estimates that in 2022 there were approximately 20 million new cancer cases and nearly 9.7 million deaths worldwide, and the adverse side effects associated with current cytotoxic treatments continue to drive the search for safer and more effective anticancer drugs. Against that backdrop, the review positions quinazoline analogs as a versatile scaffold with demonstrated efficacy in inhibiting metastasis, roles in overcoming drug resistance and potential to enhance immunotherapy efficacy. Whether the post-2018 dip in publication counts marks consolidation or decline remains an open question, but the keyword trajectory, with docking studies and quantitative potency measurements rising to prominence, suggests a field shifting from exploratory synthesis toward more quantitative, target-directed drug design.
Subject of Research: Bibliometric and pharmacological review of anticancer quinazoline research trends and synthetic approaches from 1992 to 2024
Article Title: Bibliometric analysis of research trends and synthetic approaches for anticancer quinazoline analogs from 1992 to 2024
Article References: Moghadam, F. A., Mokhtary, M., & Hozni, S. A. (2026). Bibliometric analysis of research trends and synthetic approaches for anticancer quinazoline analogs from 1992 to 2024. Discover Chemistry, 3(1), Article 595. https://doi.org/10.1007/s44371-026-01021-9
Image Credits: AI Generated
DOI: 10.1007/s44371-026-01021-9
Keywords: quinazoline, bibliometrics, anticancer, EGFR inhibitors, kinase inhibitors, structure-activity relationship, Scopus, drug discovery, synthetic chemistry, molecular docking, drug resistance, nanotechnology
News Source: Bethany Barker. (October 29, 2026). Four Decades of Anticancer Quinazoline Research Mapped in New Bibliometric Study. Scienmag.
