Abstract

A series of 4-(1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine derivatives have been depicted by one-pot three component synthesis. The synthesis involved the reaction of 4-hydroxy-2H-chromen-2-one with 1H-pyrazole-5-carbaldehydes and urea/thiourea. The reaction was conducted in the presence of L-proline as a catalyst and ethanol as the solvent. This approach exhibits notable benefits like high yields, environmental compatibility, an easy procedure, short reaction periods, and mild reaction conditions. The synthesized compounds were examined for their cytotoxicity potential in HeLa and MCF-7 cells. Among all, 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione showed promising activity with IC₅₀ values 8.0 and 8.5 µM towards MCF-7 and HeLa cells, respectively. In addition, the docking studies revealed that 4-(1,4-dimethyl-1H-pyrazol-5-yl)-3,4-dihydro-1H-chromeno[4,3-d]pyrimidine-2,5-dione had a favorable binding energy of –9.4 kcal/mol in inhibiting the human Aldo-keto reductase 1C3.

中文翻译：

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4-(1H-吡唑-5-基)-3,4-二氢-1H-色并[4,3-d]嘧啶-2,5-二酮的绿色一锅合成及其抗癌活性评价

摘要

通过一锅三组分合成法描述了一系列4-(1 H-吡唑-5-基)-3,4-二氢-1 H-色并[4,3- d ]嘧啶衍生物。该合成涉及4-羟基-2H - 2-苯并吡喃-2-酮与1H-吡唑-5-甲醛和脲/硫脲的反应。该反应在L-脯氨酸作为催化剂和乙醇作为溶剂的存在下进行。该方法具有收率高、环境相容性好、操作简单、反应周期短、反应条件温和等显着优点。检查合成的化合物在 HeLa 和 MCF-7 细胞中的细胞毒性潜力。其中，4-(1,4-二甲基-1H-吡唑-5-基)-3,4-二氢-1H-色并[4,3- d ]嘧啶-2,5-二酮表现出良好的活性对于 MCF-7 和 HeLa 细胞的IC ₅₀值分别为 8.0 和 8.5 µM。此外，对接研究表明 4-(1,4-二甲基-1 H -pyrazol-5-yl)-3,4-dihydro-1 H -chromeno[4,3- d ]pyrimidine-2,5-二酮在抑制人醛酮还原酶 1C3 方面具有 –9.4 kcal/mol 的有利结合能。