Mphahlele Malose Jack, Maluleka Marole Maria, Makhafola Tshepiso Jan, Mabeta Peace
Department of Chemistry, College of Science, Engineering and Technology, University of South Africa, P.O. Box 392, Pretoria 0003, South Africa.
Department of Life and Consumer Sciences, College of Agriculture and Environmental Sciences, University of South Africa, Private Bag X06, Florida 1710, South Africa.
Molecules. 2014 Nov 13;19(11):18527-42. doi: 10.3390/molecules191118527.
Direct one-pot base-promoted conjugate addition-elimination of 6,8-dibromo-4-chloroquinoline-3-carbaldehyde with methyl mercaptoacetate and subsequent cyclization afforded methyl [(6,8-dibromothieno[3,2-c]quinoline)]-2-carboxylate. The latter undergoes Suzuki-Miyaura cross-coupling with arylboronic acids to yield exclusively the corresponding alkyl [(6,8-diarylthieno[3,2-c]quinoline)]-2-carboxylates,. The cytotoxicity of the prepared compounds was evaluated against the human breast cancer cell line MCF-7 using the MTT assay. The effects of compounds 2, 3c and 4d on cell kinetics were further determined using the xCELLigence Real Time Cell Analysis (RTCA) system. In both the MTT assay and Real Time Cell Analysis, the compounds inhibited cancer cell growth in a dose- and time-dependent manner. Furthermore, on the basis of the calculated LC50 values, the compounds compared favourably with nocodazole, a well-established anticancer drug.
在碱促进下，6,8 - 二溴 - 4 - 氯喹啉 - 3 - 甲醛与巯基乙酸甲酯直接进行一锅法共轭加成 - 消除反应，随后环化得到[(6,8 - 二溴噻吩并[3,2 - c]喹啉)] - 2 - 羧酸甲酯。后者与芳基硼酸进行铃木 - 宫浦交叉偶联反应，仅生成相应的[(6,8 - 二芳基噻吩并[3,2 - c]喹啉)] - 2 - 羧酸烷基酯。使用MTT法评估所制备化合物对人乳腺癌细胞系MCF - 7的细胞毒性。使用xCELLigence实时细胞分析（RTCA）系统进一步测定化合物2、3c和4d对细胞动力学的影响。在MTT法和实时细胞分析中，这些化合物均以剂量和时间依赖性方式抑制癌细胞生长。此外，根据计算出的LC50值，这些化合物与已确立的抗癌药物诺考达唑相比具有优势。
