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, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240
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.
