Division of Biochemistry, Department of Studies in Chemistry, Mangalore University, Karnataka, India
Department of Studies in Industrial Chemistry, Mangalore University, Karnataka, India
Anticancer Agents Med Chem. 2020;20(14):1704-1713. doi: 10.2174/1871520620666200424102615.
Cancer is the second leading cause of mortality worldwide. Despite several advances made in the treatment strategies, the cure for cancer remains still a challenge. Currently used treatment modalities pose several side effects and remain ineffective in the later stages. Thiazolidinediones (TZDs) have been shown to possess anti-cancer activity in several in vitro models.
The objective of this study was to assess the effect of novel synthesized thiazolidinedione derivatives on three selected cancer cell lines viz., human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29). This study also aimed to evaluate the anti-inflammatory and DNA binding activity of the synthesized derivatives.
The synthesized thiazolidinedione derivatives were screened for their in vitro anti-cancer activity on the human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29) using the Methyl Thaizolyl Tetrazolium (MTT) Assay. They were also evaluated for in vitro antiinflammatory activity using albumin denaturation method, DNA binding activity and hemocompatibility.
Compounds 5a, 5b, 5d, 6c and 6d showed IC50 of 30.19, 41.56, 65.97, 60.16 and 50.41μM respectively on breast adenocarcinoma (MCF-7), IC50 of 49.75, 51.42, 65.43, 61.94 and 56.80μM on lung adenocarcinoma (A549) and 38.11, 45.58, 71.24, 53.15 and 51.25μM on colorectal carcinoma (HT29). In the hemolysis assay, compounds 5a and 5b were found to be nontoxic and nonhemolytic to human erythrocytes. Five compounds possessed significant anticancer and anti-inflammatory activity. Three of them are Mannich bases, whereas the remaining two are aryl acyl derivatives.
The in vitro results (anticancer and anti-inflammatory) showed that the 4-chloro anilinomethyl substitution at third position and thiophenoethenyl at the fifth position of thiozolidinedione (5a) emerged as the most effective derivative on all the tested cancer cell lines. A higher DNA binding affinity of the test compounds was also found.
癌症是全球第二大死亡原因。尽管在治疗策略方面取得了几项进展，但癌症的治愈仍然是一个挑战。目前使用的治疗方法存在多种副作用，并且在晚期仍然无效。噻唑烷二酮（TZDs）已在几种体外模型中显示出抗癌活性。
本研究的目的是评估新型合成噻唑烷二酮衍生物对三种选定的癌细胞系（人乳腺癌细胞系 MCF-7、肺腺癌 A549 和结直肠癌细胞系 HT29）的影响。本研究还旨在评估合成衍生物的抗炎和 DNA 结合活性。
使用 Methyl Thaizolyl Tetrazolium（MTT）测定法，对合成的噻唑烷二酮衍生物在人乳腺癌细胞系（MCF-7）、肺腺癌（A549）和结直肠癌细胞系（HT29）上的体外抗癌活性进行筛选。还使用白蛋白变性法、DNA 结合活性和血液相容性评估它们的体外抗炎活性。
化合物 5a、5b、5d、6c 和 6d 对乳腺癌（MCF-7）的 IC50 分别为 30.19、41.56、65.97、60.16 和 50.41μM，对肺腺癌（A549）的 IC50 分别为 49.75、51.42、65.43、61.94 和 56.80μM，对结直肠癌（HT29）的 IC50 分别为 38.11、45.58、71.24、53.15 和 51.25μM。在溶血试验中，发现化合物 5a 和 5b 对人红细胞既无毒性也无溶血作用。五种化合物具有显著的抗癌和抗炎活性。其中三种是曼尼希碱，其余两种是芳基酰基衍生物。
体外结果（抗癌和抗炎）表明，噻唑烷二酮（5a）的第三位置 4-氯苯胺甲基取代和第五位置噻吩乙稀基取代成为所有测试的癌细胞系中最有效的衍生物。还发现测试化合物具有更高的 DNA 结合亲和力。
