![Sample our Bioscience journals, sign in here to start your access, Latest two full volumes FREE to you for 14 days]({"type":"image" , "src" : "/sda/5925/TOC-Subject-Sample-2021-Bioscience.jpg"})
Abstract
Purpose
The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1,4-pentadien-3-ones inspired pyrazole moiety was synthesized and evaluated on their anti-colon cancer activities.
Methods
Fifteen new compounds were synthesized and characterized by spectral datum, and then they were tested preliminarily by MTT assay for their cytotoxic activities against a panel of four human cancer cell lines, namely, gastric (SGC-7901), liver (HepG2), lung (A549), and colon (SW620) cancer cells. Compound 7h exhibited excellent selectivity and outstanding anti-proliferation activity against SW620 cells among these 15 compounds. Further, the mechanisms were investigated by transwell migration and invasion assay, clonogenic assay, cell apoptosis analysis, cell cycle analysis, Western blot analysis.
Results
The IC50 value of 7h against SW620 cells was 12 nM, being more potent than curcumin (IC50 = 9.36 μM), adriamysin (IC50 = 3.28 μM) and oxaliplatin (IC50 = 13.33 μM). Further assays showed that 7h inhibited SW620 cell migration, invasion and colony formation obviously, which was due to its ability to induce cell cycle arrest in the G2/M and S phases and apoptosis. Western blot assay revealed that 7h decreased the protein expression of ATM gene, which may primarily contribute to its anticancer activity against SW620 cells.
Conclusion
A new MCACs 7h was synthesized and found to exhibit excellent anti-proliferation activity against SW620 cells. Further studies indicated that 7h exerted its anticancer activity against SW620 cells probably via decreasing the ATM protein expression. The present study suggested that 7h was a promising candidate as an anti-colon cancer drug for future development.
Acknowledgment
The financial supports by the National Natural Science Foundation of China (No. 81770377) and the Natural Science Foundation of Hubei Province (No. 2017CFB448) is gratefully acknowledged.
Abbreviations
MCACs, monocarbonyl analogs of curcumin; MTT, methyl thiazolyl tetrazolium; IC50, 50% inhibitory concentration; ATM, ataxia-telangiectasia mutated; PARP, poly ADP-ribose polymerase; CRISPR, clustered regularly interspaced short palindromic repeats; FBS, fetal calf serum.
Disclosure
The authors report no conflicts of interest in this work.