Abstract
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 IC50 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 P21 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.
Highlights
Malignant cancer is one of the leading causes of death in humans
We evaluated the anti-tumor effect on BCAP-37 and MCF-7 cells via MTT assay of nine pyrano[2,3-c]pyrazole derivatives (Figure 2, Table 1)
(hereinafter abbreviated as AMDPC) as the object of study, and explored its nanoformulation and mechanism of the Molecules 2019, 24, xeffect on the BCAP-37 cells (Table 1)
Summary
Malignant cancer is one of the leading causes of death in humans. Due to the risk of cancer to human life and health, it is always an important task for scientists to find efficient and safe anti-cancer drugs. The mainstream drugs for cancer treatment can be divided into alkylating agents, anti-metabolites, anti-tumor antibiotics, hormones, and platinum compounds according to different drug structures, sources, and different mechanisms of action on tumor cells. Because of drug resistance and the side effects, research and development of anti-cancer drugs has never stopped. Cell cycle-related genes and proteins are closely linked with the occurrence and development of tumors, and become targets for tumor treatment [1,2,3,4]. Drugs that can impact the cell cycle are expected to have an anti-tumor effect
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