We synthesized new analogues of the anti-AML agent VS-II-173. We studied the effect of the substitution at the 1- and 5-positions of the pyrazolo[4,3-a]phenanthridine scaffold on Pim-1 kinase inhibition and cytotoxicity against AML MOLM-13 cells. We found that compounds 20 and 21, substituted at the 1-position exhibited stronger Pim-1 inhibition together with a high potency toward MOLM-13 cells, associated with apoptosis induction and selectivity over non-cancerous NRK cells.

中文翻译：

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新型吡唑并[4,3-a]菲啶Pim-1抑制剂的合成及其对MOLM-13急性髓细胞白血病细胞系的细胞毒活性评价

我们合成了抗 AML 剂VS-II-173的新类似物。我们研究了吡唑并[4,3- a ]菲啶支架的 1 位和 5 位取代对 Pim-1 激酶抑制和对 AML MOLM-13 细胞的细胞毒性的影响。我们发现在 1 位取代的化合物20和21表现出更强的 Pim-1 抑制作用以及对 MOLM-13 细胞的高效力，这与细胞凋亡诱导和对非癌性 NRK 细胞的选择性有关。