Antoniolli Giorgio, Lima Keli, Franchi Gilberto Carlos, Lima Carmen Silvia Passos, Machado-Neto João Agostinho, Coelho Fernando
Institute of Chemistry, University of Campinas, Campinas, SP 13083-862, Brazil.
Faculty of Medicine, University of São Paulo, São Paulo, SP 01246-903, Brazil.
ACS Omega. 2025 Aug 1;10(31):34882-34894. doi: 10.1021/acsomega.5c04106. eCollection 2025 Aug 12.
The increasing life expectancy and rising prevalence of cancer emphasize the need for innovative therapeutic strategies. Targeted therapies have revolutionized cancer treatment by offering greater specificity and reduced toxicity compared to traditional cytotoxic drugs. Acute leukemias, including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), remain aggressive malignancies with poor outcomes, particularly in elderly patients. Despite advancements, resistance to chemotherapy and adverse effects necessitate the discovery of novel antitumor compounds. Quinazolines, a versatile class of heterocyclic compounds, exhibit diverse biological activities, including anticancer properties. In this study, 20 derivatives of 2-substituted quinazolin-4-(3)-ones were synthesized via condensation of 2-aminobenzamide with aldehydes in dimethyl sulfoxide. The compounds were characterized using IR, H NMR, and C NMR spectroscopy. Biological evaluation revealed that compounds and exhibited potent cytotoxic effects against T cell ALL (jurkat cells) and AML of promyelocytic subtype (APL) NB4 cells, with compound showing IC values below 5 μM in both cell types. Compound demonstrated selectivity for Jurkat cells. Further analyses, including apoptosis/cycle cell assays and pharmacokinetic predictions, confirmed their therapeutic potential. The data open new perspectives for "" studies concerning the application of quinazolin-4-(3)-ones in treatment of acute leukemias of lymphoid and myeloid origins.
预期寿命的增加和癌症患病率的上升凸显了创新治疗策略的必要性。与传统细胞毒性药物相比，靶向疗法通过提供更高的特异性和更低的毒性，彻底改变了癌症治疗。急性白血病，包括急性淋巴细胞白血病（ALL）和急性髓细胞白血病（AML），仍然是侵袭性恶性肿瘤，预后较差，尤其是在老年患者中。尽管取得了进展，但对化疗的耐药性和不良反应使得发现新型抗肿瘤化合物成为必要。喹唑啉是一类用途广泛的杂环化合物，具有多种生物活性，包括抗癌特性。在本研究中，通过2-氨基苯甲酰胺与醛在二甲基亚砜中缩合，合成了2-取代喹唑啉-4-（3）-酮的20种衍生物。使用红外光谱、氢核磁共振光谱和碳核磁共振光谱对这些化合物进行了表征。生物学评估显示，化合物 和 对T细胞ALL（jurkat细胞）和早幼粒细胞亚型AML（APL）NB4细胞表现出强大的细胞毒性作用，化合物 在两种细胞类型中的IC值均低于5 μM。化合物 对Jurkat细胞表现出选择性。进一步的分析，包括凋亡/细胞周期检测和药代动力学预测，证实了它们的治疗潜力。这些数据为关于喹唑啉-4-（3）-酮在治疗淋巴和髓系起源的急性白血病中的应用的“”研究开辟了新的前景。
