Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells,RSC Advances

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Synthesis of novel fatty acid 3,4-dihydropyrimidin-2-(1H)-one and antitumoral activity against breast and gastric cancer cells
RSC Advances ( IF 3.9 ) Pub Date : 2024-07-22 , DOI: 10.1039/d4ra03292f
E A M Rios ₁ , C M Dea ₁ , E R F B Dos Santos ₁ , M G M D'Oca ₂ , D S Rampon ₁ , F M Nachtigall ₃ , L S Santos ₄ , L Guzman ₅ , R Moore-Carrasco ₅ , D Rebolledo-Mira ₆ , C R M D'Oca ₁

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Monastrol is the best-known small compound from the dihydropyrimidinones/thiones (DHPMs) heterocycle family, a cell-permeable molecule recognized as an inhibitor of mitotic kinesin Eg5, that is over-expressed in tumor cells and is a very promising target for the development of new drugs for cancer. The lipophilic properties of the DHPMs have been demonstrated to be of pivotal importance in the design of new molecules. This work describes the synthesis and antitumoral activity of novel C5-substituted fatty-DHPMs against breast and gastric cancer cell lines. The compounds were synthesized via Biginelli multicomponent reaction from oleyl β-ketoester in good yields (40–72%) using a simple approach catalyzed by nontoxic and free-metal sulfamic acid. Among the compounds tested, the compound 10c, derived from 3-hydroxybenzaldehyde and urea, exhibited 77% cellular viability to normal cells (C2C12) and was selected to be evaluated against tumoral breast (MCF-7) and gastric (AGS) cell lines. The results obtained afforded an IC₅₀ of breast cancer cells of 2.3 μM, qualifying the molecule as the most potent, and making it a promising compound for future experiments in vivo.

中文翻译：

新型脂肪酸3,4-二氢嘧啶-2-(1H)-one的合成及其对乳腺癌和胃癌细胞的抗肿瘤活性

Monastrol 是二氢嘧啶酮/硫酮 (DHPM) 杂环家族中最著名的小化合物，是一种细胞渗透性分子，被认为是有丝分裂驱动蛋白 Eg5 的抑制剂，在肿瘤细胞中过度表达，是一个非常有前途的开发靶点抗癌新药。 DHPM 的亲脂特性已被证明在新分子的设计中至关重要。这项工作描述了新型 C5 取代的脂肪-DHPM 的合成及其对乳腺癌和胃癌细胞系的抗肿瘤活性。这些化合物是通过Biginelli 多组分反应从油基 β-酮酯合成的，采用无毒且游离金属氨基磺酸催化的简单方法，收率良好（40-72%）。在测试的化合物中，衍生自3-羟基苯甲醛和尿素的化合物10c对正常细胞(C2C12)表现出77%的细胞活力，并被选择用于针对肿瘤乳腺(MCF-7)和胃(AGS)细胞系进行评估。获得的结果显示乳腺癌细胞的 IC ₅₀为 2.3 μM，证明该分子是最有效的分子，并使其成为未来体内实验有前途的化合物。

更新日期：2024-07-22

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