Synthesis and biological evaluation of novel fused pyridopyrimidine derivatives as topoisomerase I inhibitors and as potential antitumor agents: promising results in lung, ovary and gastric cancer
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Le résumé fourni par la source
ABSTRACT. The topoisomerase I (TOP1) enzymatic inhibition was investigated using novel pyrimidine and quinazolinone derivatives. First, the synthesis of these compounds was performed by intramolecular cycloaddition reaction of functionalized aminoalcohols, aminoesters and aldimines, obtained by the condensation of 2-aminopyridine and unsaturated aldehydes, affording corresponding pyrido[1,2- a ]pyrimidine derivatives, pyrido[2,1- b ]quinazolin-11-one derivatives and hybrid chromeno[4,3- d ]pyrido[1,2- a ]pyrimidine compounds respectively with good to high general yields. The vast majority of prepared products showed notable and excellent activity as inhibitors of TOP1. The cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549), human ovarian carcinoma (SKOV-3), human gastric adenocarcinoma (AGS), human undifferentiated gastric adenocarcinoma derived from the metastatic lymph node (HGC27), and on non-cancerous lung fibroblasts cell line (MRC-5) was also screened. Dihydrochromeno[4,3- d ]pyrido[1,2- a ]pyrimidine 9b was the most cytotoxic compound with IC 50 values of 6.0±0.3 nM in the A549 cell line, and with IC 50 values of 4.67±0.02 μM in the SKOV-3 cell line. Compound 9p (LL123) also proved to be a good candidate in two human gastric carcinoma lines (HGC27 and AGS). Furthermore, none of the compounds with outstanding results showed toxicity against non-malignant lung fibroblasts (MRC-5).
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Synthesis and biological evaluation of novel fused pyridopyrimidine derivatives as topoisomerase I inhibitors and as potential antitumor agents: promising results in lung, ovary and gastric cancer
- Date Crossref
- 01/06/2026
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of the Basque Country pays non établi dans la noticeUniversité ou école supérieure
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Aarhus University Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center (iNANO) pays non établi dans la noticeUniversité ou école supérieure
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Gastroenterology Hospital "Saverio de Bellis" pays non établi dans la noticeÉtablissement de santé
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University of Bari Aldo Moro pays non établi dans la noticeUniversité ou école supérieure
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Faculty of Pharmacy and Lascaray Research Center Organic Chemistry I Department pays non établi dans la noticeUniversité ou école supérieure
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National Institute of Gastroenterology pays non établi dans la noticeStructure de recherche
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University of Bari "A. Moro" Department of Pharmacy - Drug Sciences pays non établi dans la noticeUniversité ou école supérieure
University of the Basque Country, Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center (iNANO) — Aarhus University et Gastroenterology Hospital "Saverio de Bellis", avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.