Synthesis, Antiproliferative, and Multidrug Resistance Reversal Activities of Heterocyclic α,β-Unsaturated Carbonyl Compounds.
A series of heterocyclic α,β-unsaturated carbonyl compounds (1a-1d, 2a-2d, 3a-3d, 4a-3d, and 5a-5d) with 1,5-diaryl-3-oxo-1,4-pentadienyl pharmacophore were synthesized for the development of anticancer and multidrug resistance reverting agents. The antiproliferative activities were tested against nine human cancer cell lines. Approximately 73% of the IC50 values were below 5 μm, while 35% of these figures were submicromolar, and compounds 3a-3d with 4-trifluoro methyl in the arylidene benzene rings were the most potent, since their IC50 values are between 0.06 and 3.09 μm against all cancer cell lines employed. Meanwhile, their multidrug resistance reversal properties and cellular uptake were further examined. The data displayed that all of these compounds could reverse multidrug resistance, particularly, compounds 3a and 4a demonstrated both potent multidrug resistance reverting properties and strong antiproliferative activities, which can be taken as leading molecules for further research of dual effect agents in tumor chemotherapy.
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China. sjf.xzy@163.com.
Ju-Feng
JF
Sun
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China.
Gui-Ge
GG
Hou
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China.
Feng
F
Zhao
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China.
Wei
W
Cong
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China.
Hong-Juan
HJ
Li
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China.
Wen-Shuai
WS
Liu
School of Pharmacy, Binzhou Medical University, Yantai, Shandong, 264003, China. chunhuawang508@126.com.
Chunhua
C
Wang
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D060888:Real-Time Polymerase Chain Reaction
D000970:Antineoplastic Agents; D003374:Coumarins; D005419:Flavonoids; D006571:Heterocyclic Compounds; C030123:coumarin
4-Piperidones; antiproliferative activity; heterocyclic; multidrug resistance reversal activity; α,β-Unsaturated carbonyl compounds