Gomha Sobhi M, Abdallah Magda A, Abbas Ikhlass M, Kazem Mariam S H
Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Department of Chemistry, Faculty of Dentistry, October University for Modern Science & Arts University, Giza, 12613, Egypt.
Med Chem. 2018;14(4):344-355. doi: 10.2174/1573406413666171020114105.
Chalcones, 2-pyrazolines and thiazoles have been reported to possess various pharmacological activities.
Synthesis of new chalcones and utilizing them as a building block for constructing a series of thiazole derivatives and evaluating some of them as anticancer agents.
The new compounds were synthesized via stirring at room temperature or thermal heating. Cytotoxic evaluation of the new synthesized compounds was tested using the method of Skehan et al. Moreover, the computational studies were performed using MOE 2014.09 software.
A series of new chalcones were prepared by the reaction of ethyl 3-acetyl-1-aryl-5-methyl- 1H-pyrazole-4-carboxylate with a number of substituted benzaldehydes. One of these chalcones was used as a building block for constructing a pyrazoline ring via its reaction with thiosemicarbazide. The produced carbothioamide derivative was used for the preparation of two series of thiazole derivatives by its reaction with a number of hydrazonoyl chlorides. Moreover, reaction of 3- acetylpyrazole thiosemicarbazone derivative with a number of N-aryl-2-oxopropane hydrazonoyl chlorides afforded 5-arylazothiazole derivatives. The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data. Some of the newly synthesized chalcones and thiazoles were tested for their cytotoxicity against human colon carcinoma cell line (HCT-116) and the molecular docking was carried out on the most active compound 3f.
The results of the anticancer activity revealed that compounds 3f, 3e, 3c and 3b have promising activities compared with the standard drug Doxorubicin. Moreover, the computational studies confirm the results of biological activity. Also, the ADME profile study showed that compound 3f can be considered as a promising drug by conducting good pharmacokinetic and medicinal chemistry tests.
据报道，查耳酮、2-吡唑啉和噻唑具有多种药理活性。
合成新型查耳酮，并将其用作构建一系列噻唑衍生物的基础单元，同时评估其中一些化合物作为抗癌剂的活性。
通过室温搅拌或加热合成新化合物。采用Skehan等人的方法对新合成化合物进行细胞毒性评估。此外，使用MOE 2014.09软件进行计算研究。
通过3-乙酰基-1-芳基-5-甲基-1H-吡唑-4-羧酸乙酯与多种取代苯甲醛反应制备了一系列新型查耳酮。其中一种查耳酮通过与硫代氨基脲反应用作构建吡唑啉环的基础单元。所生成的碳硫酰胺衍生物通过与多种肼基酰氯反应用于制备两个系列的噻唑衍生物。此外，3-乙酰基吡唑硫代氨基脲衍生物与多种N-芳基-2-氧代丙烷肼基酰氯反应得到5-芳基偶氮噻唑衍生物。所有新合成化合物的指定结构均基于元素分析和光谱数据得到证实。对一些新合成的查耳酮和噻唑进行了针对人结肠癌细胞系（HCT-116）的细胞毒性测试，并对活性最高的化合物3f进行了分子对接。
抗癌活性结果表明，与标准药物阿霉素相比，化合物3f、3e、3c和3b具有良好的活性。此外，计算研究证实了生物活性结果。同时，药物代谢动力学和药物化学性质研究表明，通过良好的药代动力学和药物化学测试，化合物3f可被视为一种有前景的药物。
