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


METHODS
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.


CONCLUSIONS
Thus, these compounds with the potent anticancer activity and low toxicity have potential for the development of new anticancer chemotherapy agents.
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Xiaoping
X
Zhan
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Weixi
W
Qin
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Shuai
S
Wang
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Kai
K
Zhao
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Yuxuan
Y
Xin
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Yaolin
Y
Wang
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Qi
Q
Qi
School of Pharmacy, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai 200240, China.
Zhenmin
Z
Mao
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016466:CHO Cells; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D045744:Cell Line, Tumor; D006224:Cricetinae; D003412:Cricetulus; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066244:Proton Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D011758:Pyrroles
MTT assay; Pyrrole derivatives; anticancer activity; benzoyl-4-substituted; cytotoxicity; synthesis