Title:Synthesis and Anti-cancer Activity of 3-substituted Benzoyl-4-substituted Phenyl-1H-pyrrole Derivatives
Volume: 17
Issue: 6
Author(s): Xiaoping Zhan, Weixi Qin, Shuai Wang, Kai Zhao, Yuxuan Xin, Yaolin Wang, Qi Qi and Zhenmin Mao*
Affiliation:
- School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240,China
Keywords:
Pyrrole derivatives, anticancer activity, synthesis, MTT assay, cytotoxicity, benzoyl-4-substituted.
Abstract: Background: Cancer is considered a major public health problem worldwide.
Objective: The aim of this paper is to design and synthesis of novel anticancer agents with potent anticancer
activity and minimum side effects. Method: A series of pyrrole derivatives were synthesized, their anti-cancer
activity against nine cancer cell lines and two non-cancer cell lines were evaluated by MTT assay, and their cell
cycle progression were determined by flow cytometry analysis.
Results: The study of the structure-activity relationships revealed that the introduction of the electron-donation
groups at the 4th position of the pyrrole ring increased the anti-cancer activity. Among the synthesized
compounds, specially the compounds bearing 3,4-dimethoxy phenyl at the 4th position of the pyrrole ring showed
potent anti-cancer activity, cpd 19 was the most potent against MGC 80-3, HCT-116 and CHO cell lines (IC50s =
1.0－1.7 μM), cpd 21 was the most potent against HepG2, DU145 and CT-26 cell lines (IC50s = 0.5－0.9 μM),
and cpd 15 was the most potent against A549 (IC50 = 3.6 μM). Moreover, these potent compounds showed weak
cytotoxicity against HUVEC and NIH/3T3. Thus, the cpds 15, 19 and 21 show potential anti-cancer for further
investigation. Furthermore, the flow cytometry analysis revealed that cpd 21 arrested the CT-26 cells at S phase,
and induced the cell apoptosis.
Conclusion: Thus, these compounds with the potent anticancer activity and low toxicity have potential for the
development of new anticancer chemotherapy agents.
