Aboelmagd Ahmed, El Rayes Samir M, Gomaa Mohamed S, Fathalla Walid, Ali Ibrahim A I, Nafie Mohamed S, Pottoo Faheem H, Khan Firdos Alam, Ibrahim Mohamed M
Department of Chemistry, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt.
Department of Pharmaceutical, College of Clinical Pharmacy, ImamAbdulrahman Bin Faisal University, P. O. Box 1982, Dammam 31441, Kingdom of Saudi Arabia.
ACS Omega. 2021 Feb 15;6(8):5244-5254. doi: 10.1021/acsomega.0c05263. eCollection 2021 Mar 2.
Several metal complexes of methyl-3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoate derivatives were synthesized and tested for their anti-tumor activities. The ligands include 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanoic acid (), 3-(4-chlorophenyl)-3-hydroxy-2,2-dimethylpropanehydrazide (), and 3-(4-chlorophenyl)-'-(4-(dimethylamino)benzylidene)-3-hydroxy-2,2-dimethylpropanehydrazide (). The ligands were reacted with Cu (II), Ni (II), and La (III) ions. The formed complexes were characterized using elemental analysis (M%), molar conductivity in DMF (0.001 M), DTA, TG, FTIR, ICP-AES, and magnetic susceptibility. The chemical structures of the obtained complexes were interpreted, and their chemical formulas were postulated. The anti-cancer activities of these complexes were examined on human colorectal carcinoma cells (HCT-116) and also on normal cells (HEK-293). The 48 h post treatments showed that out of 12 compounds, 10 compounds showed inhibitory actions on HCT-116 cells, whereas two compounds did not show any inhibitory actions. Compounds and showed the highest inhibitory actions with IC = 0.154 and 0.18 mM and additionally compounds , , and with IC = 0.267, 0.205, and 0.284 mM, respectively. All tested compounds did not show any inhibitory action on normal HEK-293 cells. Molecular docking results provided a good evidence for activity of the lead compounds and as CDK8-CYCC kinase inhibitors, which may proposed the mechanism of action toward colon cancer therapy.
合成了几种3-(4-氯苯基)-3-羟基-2,2-二甲基丙酸甲酯衍生物的金属配合物，并对其抗肿瘤活性进行了测试。配体包括3-(4-氯苯基)-3-羟基-2,2-二甲基丙酸、3-(4-氯苯基)-3-羟基-2,2-二甲基丙烷酰肼和3-(4-氯苯基)-α-(4-(二甲氨基)亚苄基)-3-羟基-2,2-二甲基丙烷酰肼。这些配体与铜(II)、镍(II)和镧(III)离子反应。通过元素分析(M%)、在DMF(0.001 M)中的摩尔电导率、差示热分析、热重分析、傅里叶变换红外光谱、电感耦合等离子体原子发射光谱和磁化率对形成的配合物进行了表征。对所得配合物的化学结构进行了解释，并推测了它们的化学式。在人结肠癌细胞(HCT-116)和正常细胞(HEK-293)上检测了这些配合物的抗癌活性。处理48小时后显示，在12种化合物中，10种化合物对HCT-116细胞有抑制作用，而两种化合物没有任何抑制作用。化合物 和 表现出最高的抑制作用，IC50分别为0.154和0.18 mM，此外化合物 、 和 的IC50分别为0.267、0.205和0.284 mM。所有测试化合物对正常HEK-293细胞均未显示任何抑制作用。分子对接结果为先导化合物 和 作为CDK8-CYCC激酶抑制剂的活性提供了有力证据，这可能揭示了其对结肠癌治疗的作用机制。
