Research Article

Synthesis and Anti-cancer Activity of 3-substituted Benzoyl-4-substituted Phenyl-1H-pyrrole Derivatives

Author(s):

Xiaoping Zhan, Weixi Qin, Shuai Wang, Kai Zhao, Yuxuan Xin, Yaolin Wang, Qi Qi and Zhenmin Mao*   Pages 821 - 831 ( 11 )

Abstract:

Background: Cancer is considered a major public health problem worldwide. <p></p> 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. <p></p> 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. <p></p> Conclusion: Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents. <p></p>

Keywords:

Pyrrole derivatives, anticancer activity, synthesis, MTT assay, cytotoxicity, benzoyl-4-substituted.

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

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