Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China.
Molecules. 2019 Feb 11;24(3):624. doi: 10.3390/molecules24030624.
Pyrano[2,3-c]pyrazole derivatives have been reported as exerting various biological activities. One compound with potential anti-tumor activity was screened out by MTT assay from series of dihydropyrazopyrazole derivatives we had synthesized before using a one-pot, four-component reaction, and was named as 6-amino-4-(2-hydroxyphenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (hereinafter abbreviated as AMDPC). The IC of AMDPC against Bcap-37 breast cancer cells was 46.52 μg/mL. Then the hydrophobic AMDPC was encapsulated in PEG-PLGA block copolymers, and then self-assembled as polymeric micelle (mPEG-PLGA/AMDPC) to improve both physiochemical and release profiles. The effect of mPEG-PLGA/AMDPC on BCAP-37 cancer cells showed similar anti-tumor effects as AMDPC. Furthermore, the anti-tumor mechanism of mPEG-PLGA/AMDPC was investigated, which can probably be attributed to stimulating the expression of gene and therefore protein production on BCAP-37 cells, and then blocked the cell cycle through the P53-independent pathway both in S phase and G2 phase. Thus, mPEG-PLGA/AMDPC is a promising therapeutic agent for cancer treatment, and further in vivo studies will be developed.
吡唑并[2,3-c]吡唑衍生物已被报道具有多种生物活性。我们之前曾通过一锅四组分反应合成了一系列二氢吡唑并吡唑衍生物，并用 MTT 法从中筛选出一种具有潜在抗肿瘤活性的化合物，命名为 6-氨基-4-(2-羟基苯基)-3-甲基-1,4-二氢吡喃并[2,3-c]吡唑-5-甲腈（以下简称 AMDPC）。AMDPC 对乳腺癌细胞 Bcap-37 的 IC 为 46.52 μg/mL。然后将疏水性 AMDPC 包封在 PEG-PLGA 嵌段共聚物中，然后自组装成聚合物胶束（mPEG-PLGA/AMDPC），以改善其理化性质和释放特性。mPEG-PLGA/AMDPC 对 BCAP-37 癌细胞的作用显示出与 AMDPC 相似的抗肿瘤作用。此外，还研究了 mPEG-PLGA/AMDPC 的抗肿瘤机制，可能归因于刺激 BCAP-37 细胞基因的表达，从而增加蛋白的产生，并通过 P53 非依赖性途径在 S 期和 G2 期阻断细胞周期。因此，mPEG-PLGA/AMDPC 是一种有前途的癌症治疗药物，将进一步开展体内研究。
