二氢嘧啶与哒嗪酮杂合物作为潜在抗乳腺癌药物的合成
Synthesis of Hybrids of Dihydropyrimidine and Pyridazinone as potential Anti-Breast Cancer Agents.
作者信息
Akhtar Wasim, Verma Garima, Khan Mohemmed Faraz, Shaquiquzzaman Mohammad, Rana Arpana, Anwer Tarique, Akhter Mymoona, Alam M Mumtaz
机构信息
Drug Design and Medicinal Chemistry Lab, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi 110062, India.
Advanced Institute of Pharmacy, Palwal, Haryana 121105. India.
出版信息
Mini Rev Med Chem. 2018;18(4):369-379. doi: 10.2174/1389557517666170220153456.
BACKGROUND
Different 3-aroylpropionic acids and dihydropyrimidine hydrazine derivatives were condensed together to yield a series of dihydropyrimidine and pyridazinone hybrids (5a-u).
OBJECTIVE
This was done in order to develop therapeutic agents for the treatment of breast cancer with improved Cycloxygenase-2 (COX-2) selectivity. In-vitro anticancer evaluation for these compounds was done against human breast cancer cell lines (MCF-7, MDA-MB-231) and normal human keratinocytes (HaCaT).
CONCLUSION
Amongst all the developed analogs, compound 5l emerged as the most potent agent against both these cell lines with IC50 values of 3.43 and 2.56 µM respectively. The synthesized compounds were also evaluated for COX-2 selectivity. To observe the binding pattern of the compounds with COX-2, a docking study was performed using PDB ID: 1CX2.
背景
将不同的3-芳酰基丙酸和二氢嘧啶肼衍生物缩合在一起，得到了一系列二氢嘧啶和哒嗪酮杂化物（5a - u）。
目的
这样做是为了开发具有更高环氧化酶-2（COX-2）选择性的乳腺癌治疗药物。对这些化合物进行了针对人乳腺癌细胞系（MCF-7、MDA-MB-231）和正常人角质形成细胞（HaCaT）的体外抗癌评估。
结论
在所有开发的类似物中，化合物5l对这两种细胞系均表现出最强活性，IC50值分别为3.43和2.56 μM。还对合成的化合物进行了COX-2选择性评估。为了观察化合物与COX-2的结合模式，使用PDB ID：1CX2进行了对接研究。
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