Vala Ruturajsinh M, Sharma Mayank G, Patel Divyang M, Puerta Adrián, Padrón José M, Ramkumar Venkatachalam, Gardas Ramesh L, Patel Hitendra M
Department of Chemistry, Sardar Patel University, Vallabh Vidyanagar, Gujarat, India.
BioLab, Instituto Universitario de Bio-Orgánica Antonio González (IUBO-AG), Universidad de La Laguna, La Laguna, Spain.
Arch Pharm (Weinheim). 2021 Jun;354(6):e2000466. doi: 10.1002/ardp.202000466. Epub 2021 Feb 15.
In this study, we report on antiproliferative benzyloxy dihydropyrimidinones (DHPMs) produced by the Biginelli reaction of benzyloxy benzaldehyde, urea, and diverse 1,3-diones. The reaction was catalyzed by lanthanum triflate and completed within 1-1.5 h, with 74-97% yield. The antiproliferative assay was carried out for all synthesized dihydropyrimidinones against six human solid tumor cell lines. Six compounds showed good antiproliferative activity with GI values below 5 μM. Among all the synthesized compounds, the most potent derivative showed good antiproliferative activity against all cell lines with GI values in the range of 1.1-3.1 μM. These DHPMs comply with druglikeness. Furthermore, ADMET prediction and the effect of P-glycoprotein on the antiproliferative activity were also studied. Overall, our method allows eco-friendly access to benzyloxy DHPMs as potential anticancer drugs.
在本研究中，我们报道了由苄氧基苯甲醛、尿素和多种1,3 - 二酮通过Biginelli反应制备的具有抗增殖活性的苄氧基二氢嘧啶酮（DHPMs）。该反应由三氟甲磺酸镧催化，在1 - 1.5小时内完成，产率为74 - 97%。对所有合成的二氢嘧啶酮针对六种人类实体瘤细胞系进行了抗增殖测定。六种化合物表现出良好的抗增殖活性，GI值低于5 μM。在所有合成化合物中，最有效的衍生物对所有细胞系均表现出良好的抗增殖活性，GI值在1.1 - 3.1 μM范围内。这些DHPMs符合类药性质。此外，还研究了ADMET预测以及P - 糖蛋白对抗增殖活性的影响。总体而言，我们的方法能够以环保的方式获得作为潜在抗癌药物的苄氧基DHPMs。
