Combining a solution-phase derived library with in-situ cellular bioassay: prompt screening of amide-forming minilibraries using MTT assay.
We constructed a minilibrary using a solution-phase synthesis through coupling of three core amino compounds (5'-amino-5'-deoxy uridine, 5'-amino-2',5'-di-deoxy arabinosyl uridine, and butan-1-amine) with 30 carboxylic acids via amide bond formation. The simplified structural core compound butan-1-amine was selectively coupled with 9 carboxylic acids as control. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay of the crude mixtures showed that analogues derived from fenbufen, butylfenbufen C15; ethacrynic acid, butyl ethacrynic amide C18; and sphingosines, Sph-1, Sph-2 and U27 had an increased cytotoxicity against MCF-7 cells as well as A549 cells. Structural elucidation with molecular docking suggested that cytotoxicity of these compounds is mainly due to the inhibition of enzymes regulating cellular apoptosis.
Chiang
Li-Wu
LW
Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University.
Pei
Kai
K
Chen
Shao-Wei
SW
Huang
Ho-Lien
HL
Lin
Kun-Ju
KJ
Yen
Tzu-Chen
TC
Yu
Chung-Shan
CS
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols; D045744:Cell Line, Tumor; D002945:Cisplatin; D020650:Combinatorial Chemistry Techniques; D007069:Ifosfamide; D016685:Mitomycin; D008958:Models, Molecular; D015394:Molecular Structure; D054852:Small Molecule Libraries
D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D016685:Mitomycin; D002945:Cisplatin; D007069:Ifosfamide