College of Pharmacy, Guizhou University, Guiyang 550025, China.
State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China.
Molecules. 2022 Jun 19;27(12):3934. doi: 10.3390/molecules27123934.
Thirty-three benzophenanthridine alkaloid derivatives (- and -) were synthesized, and their cytotoxic activities against two leukemia cell lines (Jurkat Clone E6-1 and THP-1) were evaluated in vitro using a Cell Counting Kit-8 (CCK-8) assay. Nine of these derivatives (-, and -) with IC values in the range of 0.18-7.94 μM showed significant inhibitory effects on the proliferation of both cancer cell lines. Analysis of the primary structure-activity relationships revealed that different substituent groups at the C-6 position might have an effect on the antileukemia activity of the corresponding compounds. In addition, the groups at the C-7 and C-8 positions could influence the antileukemia activity. Among these compounds, showed the strongest in vitro antiproliferative activity against Jurkat Clone E6-1 and THP-1 cells with good IC values (0.52 ± 0.03 μM and 0.48 ± 0.03 μM, respectively), slightly induced apoptosis, and arrested the cell-cycle, all of which suggests that compound may represent a potentially useful start point to undergo further optimization toward a lead compound.
合成了 33 种苯并菲啶生物碱衍生物（-和-），并采用 Cell Counting Kit-8（CCK-8）法评估了它们对两种白血病细胞系（Jurkat Clone E6-1 和 THP-1）的体外细胞毒性。其中 9 种衍生物（-、-和-）的 IC 值在 0.18-7.94 μM 范围内，对两种癌细胞系的增殖均表现出显著的抑制作用。对构效关系的初步分析表明，C-6 位的不同取代基可能对相应化合物的抗白血病活性有影响。此外，C-7 和 C-8 位的取代基也可能影响抗白血病活性。在这些化合物中，-对 Jurkat Clone E6-1 和 THP-1 细胞的体外增殖活性最强，IC 值分别为 0.52 ± 0.03 μM 和 0.48 ± 0.03 μM，轻微诱导细胞凋亡，并使细胞周期停滞，这表明化合物-可能是一个潜在有用的起始点，可进一步优化成先导化合物。
