Anti-cancer activity of heteroaromatic acetals of andrographolide and its isomers.
Anti-cancer activity of heteroaromatic acetals of andrographolide and its isomers.
复制标题
DOI：
10.1039/d2nj01055k
复制
发表时间：
2022-05-24
影响因子：
3.3
通讯作者：
Karanam, Balasubramanyam
中科院分区：
文献类型：
--
作者：
Tamang, Nitesh;Andrews, Christopher;Mavileti, Sai Kiran;Nanduri, Srinivas;Golakoti, Nageswara Rao;Karanam, Balasubramanyam
以苯甲醛和杂芳醛为原料合成了穿心莲内酯(1)、14-脱氧-12-羟基穿心莲内酯(4)和异穿心莲内酯(5)的缩醛(2a-d、3a-d和6a-d)。用1H-核磁共振、13C-核磁共振、质谱学、紫外可见光谱和红外光谱对合成的化合物进行了表征。通过单晶X-射线衍射法对化合物6d进行了表征。所有化合物都对60个NCI细胞株进行了测试。穿心莲内酯(1)的缩醛(2a-d)比12-羟基穿心莲内酯(4)和异穿心莲内酯(5)的缩醛(3a-d和6a-d)具有更好的活性。初步研究表明，使用苯甲醛合成的缩醛可以提高抗癌活性。化合物2a对白血病细胞株CCRF-CEM的生长抑制率最高，为90.97%。穿心莲内酯和七个选定的化合物对MDA-MB-231乳腺癌细胞株进行了测试。化合物3b活性最强，其IC50值为3μM。此外，对该化合物3b进行了细胞周期分析和蛋白质表达，通过破坏线粒体电位膜(Δψm)来确认细胞凋亡。
Acetals (2a–d, 3a–d, and 6a–d) of andrographolide (1), 14-deoxy-12-hydroxyandrographolide (4), and isoandrographolide (5) were synthesized using benzaldehyde and heteroaromatic aldehydes. All the synthesized derivatives were characterized using 1H-NMR, 13C-NMR, mass spectrometry, UV, and IR. The compound 6d was characterized via a single-crystal X-ray diffraction study. All the compounds were tested against 60 cell lines of NCI. The acetals (2a–d) of andrographolide (1) exhibited better activity than the acetals (3a–d, and 6a–d) of 12-hydroxyandrographolide (4) and isoandrographolide (5). Preliminary studies suggested that acetals synthesized using benzaldehyde improved anticancer activity. Compound 2a showed the highest growth inhibition of 90.97% against the leukaemia cancer cell line CCRF-CEM. Andrographolide and seven selected compounds were tested against the MDA-MB-231 breast cancer cell line. Compound 3b showed the best activity with an IC50 value of 3 μM among all the tested compounds. Furthermore, this compound 3b was subjected to cell cycle analysis and protein expression confirming apoptosis through the disruption of the mitochondrial potential membrane (Δψm).