Synthesis and Cytotoxic Activity on Human Cancer Cells of Novel Isoquinolinequinone-Amino Acid Derivatives.
A variety of aminoisoquinoline-5,8-quinones bearing α-amino acids moieties were synthesized from 3-methyl-4-methoxycarbonylisoquinoline-5,8-quinone and diverse l- and d-α-amino acid methyl esters. The members of the series were evaluated for their cytotoxic activity against normal and cancer cell lines by using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay. From the current investigation, structure-activity relationships demonstrate that the location and structure of the amino acid fragment plays a significant role in the cytotoxic effects. Moderate to high cytotoxic activity was observed and four members, derived from l-alanine, l-leucine, l-phenylalanine, and d-phenylalanine, were selected as promising compounds by their IC50 ranging from 0.5 to 6.25 μM and also by their good selectivity indexes (≥2.24).
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. jaimeadolfov@gmail.com.|Instituto de Ciencias Exactas y Naturales Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. jaimeadolfov@gmail.com.
Jaime A
JA
Valderrama
Facultad de Química, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 26094411, Chile. vcdelgad@uc.cl.
Virginia
V
Delgado
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. sandra.sepulveda.ordenes@gmail.com.
Sandra
S
Sepúlveda
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. juliob@unap.cl.|Instituto de Ciencias Exactas y Naturales Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. juliob@unap.cl.
Julio
J
Benites
Facultad de Ciencias de la Salud, Universidad de Talca, Talca 3460000, Chile. ctheodul@utalca.cl.
Cristina
C
Theoduloz
Facultad de Ciencias de la Salud, Universidad Arturo Prat, Casilla 121, Iquique 1100000, Chile. pedro.buccalderon@uclouvain.be.|Research Group of Toxicology and Cancer Biology, Louvain Drug Research Institute, Université Catholique de Louvain, 73 Avenue E. Mounier, GTOX 7309, Brussels 1200, Belgium. pedro.buccalderon@uclouvain.be.
Pedro
P
Buc Calderon
Bioanalysis and Pharmacology of Bioactive Lipids Laboratory, Louvain Drug Research Institute, Université Catholique de Louvain, 72 Avenue E. Mounier, BPBL 7201, Brussels 1200, Belgium. giulio.muccioli@uclouvain.be.
Giulio G
GG
Muccioli
D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000596:Amino Acids; D000970:Antineoplastic Agents; D003603:Cytotoxins; D015363:Quinolones
cytotoxic activity; isoquinolinequinones; tumor cell lines; α-amino acid methyl ester