Gomha Sobhi M, Abdelaziz Mohamad R, Kheder Nabila A, Abdel-Aziz Hassan M, Alterary Seham, Mabkhot Yahia N
Department of Chemistry, Faculty of Science, Cairo University, Giza, 12613, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, MIU University, Cairo, Egypt.
Chem Cent J. 2017 Oct 16;11(1):105. doi: 10.1186/s13065-017-0335-8.
Many heterocyclic compounds containing thiazole or 1,3,4-thiadiazole ring in their skeletons have been reported to possess various pharmacological activities especially anticancer activities.
4-Methyl-2-phenylthiazole-5-carbohydrazide (2) was used as a synthon to prepare 2-(4-methyl-2-phenylthiazole-5-carbonyl)-N-phenylhydrazinecarbothioamide (3) and 2-(2-(4-methyl-2-phenylthiazole-5-carbonyl)hydrazono)-N'-phenylpropane hydrazonoyl chlorides 5a-c. In addition, thioamide 3 was used as starting material for preparation of a new series of thiadiazole derivatives via its reaction with hydrazonoyl chlorides 5a-c in dioxane using triethylamines as catalyst. In addition, a series of thiazole derivatives was synthesized by reaction of thioamide 3 with a number of α-halo compounds, namely, 3-chloropentane-2,4-dione (8) or 2-chloro-3-oxo-N-phenyl butanamide (10) phenacyl bromide 12 ethyl chloroacetate (14) in EtOH in the presence of triethylamine. The structures assigned for all the new products were elucidated based on both elemental analyses and spectral data and the mechanisms of their formation was also discussed. Moreover, the new products was evaluated in vitro by MTT assays for their anticancer activity against cell lines of Hepatocellular carcinoma cell line (HepG-2). The best result observed for compounds 7b (IC = 1.61 ± 1.92 (μg/mL)) and 11 (IC = 1.98 ± 1.22 (μg/mL)). The structure-activity relationships have been suggested based on their anticancer results.
A novel series of new pharmacophores containing thiazole moiety have been synthesized using a facile and convenient methods and evaluated as potent anticancer agents.
据报道，许多骨架中含有噻唑或1,3,4 - 噻二唑环的杂环化合物具有多种药理活性，尤其是抗癌活性。
4 - 甲基 - 2 - 苯基噻唑 - 5 - 碳酰肼（2）用作合成子，制备了2 - （4 - 甲基 - 2 - 苯基噻唑 - 5 - 羰基） - N - 苯基肼基硫代甲酰胺（3）和2 - （2 - （4 - 甲基 - 2 - 苯基噻唑 - 5 - 羰基）肼基） - N'-苯基丙烷肼基酰氯5a - c。此外，硫代酰胺3用作起始原料，通过在二氧六环中以三乙胺为催化剂与肼基酰氯5a - c反应制备一系列新的噻二唑衍生物。此外，硫代酰胺3与多种α - 卤代化合物，即3 - 氯戊烷 - 2,4 - 二酮（8）或2 - 氯 - 3 - 氧代 - N - 苯基丁酰胺（10）、苯甲酰溴12、氯乙酸乙酯（14）在乙醇中，在三乙胺存在下反应，合成了一系列噻唑衍生物。基于元素分析和光谱数据阐明了所有新产物的结构，并讨论了它们的形成机制。此外，通过MTT法对新产物进行体外评估，以检测其对肝癌细胞系（HepG - 2）细胞系的抗癌活性。化合物7b（IC = 1.61±1.92（μg/mL））和11（IC = 1.98±1.22（μg/mL））观察到最佳结果。基于它们的抗癌结果提出了构效关系。
使用简便易行的方法合成了一系列含有噻唑部分的新型药效基团，并将其评估为有效的抗癌剂。
