title: Synthesis and evaluation of the cytotoxic activity of 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles in myeloid and lymphoid leukemia cell lines.
abstract: Leukemia is the most common blood cancer, and its development starts at diverse points, leading to distinct subtypes that respond differently to therapy. This heterogeneity is rarely taken into account in therapies, so it is still essential to look for new specific drugs for leukemia subtypes or even for therapy-resistant cases. Naphthoquinones (NQ) are considered privileged structures in medicinal chemistry due to their plethora of biological activities, including antimicrobial and anticancer effects. Nitrogen-containing heterocycles such as 1,2,3-1H-triazoles have been identified as general scaffolds for generating glycosidase inhibitors. In the present study, the NQ and 1,2,3-1H-triazole cores have been combined to chemically synthesize 18 new 1,2-furanonaphthoquinones tethered to 1,2,3-1H-triazoles (1,2-FNQT). Their cytotoxicities were evaluated against four different leukemia cell lines, including MOLT-4 and CEM (lymphoid cell lines) and K562 and KG1 (myeloid cell lines), as well as normal human peripheral blood mononucleated cells (PBMCs). The new 1,2-FNQT series showed high cytotoxic potential against all leukemia cell lines tested, and some compounds (12o and 12p) showed even better results than the classical therapeutic compounds such as doxorubicin or cisplatin. Others compounds, such as 12b, are promising because of their high selectivity against lymphoblastic leukemia and their low activity against normal hematopoietic cells. The cells of lymphoid origin (MOLT and CEM) were generally more sensitive than the myeloid cell lines to this series of compounds, and most of the compounds that showed the highest cytotoxicity were similarly active against both cell lines.
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Mariana F C
authors: MF
authors: Cardoso
authors: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360, Rio de Janeiro, RJ, Brazil.
authors: Patrícia C
authors: PC
authors: Rodrigues
authors: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360, Rio de Janeiro, RJ, Brazil.
authors: Maria Eduarda I M
authors: ME
authors: Oliveira
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Ivson L
authors: IL
authors: Gama
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Illana M C B
authors: IM
authors: da Silva
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Isabela O
authors: IO
authors: Santos
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: David R
authors: DR
authors: Rocha
authors: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Imunologia Clínica, 21040-360, Rio de Janeiro, RJ, Brazil.
authors: Rosa T
authors: RT
authors: Pinho
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Vitor F
authors: VF
authors: Ferreira
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil.
authors: Maria Cecília B V
authors: MC
authors: de Souza
authors: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, Campus do Valonguinho, 24210-141, Niterói, RJ, Brazil. Electronic address: gqofernando@vm.uff.br.
authors: Fernando de C
authors: Fde C
authors: da Silva
authors: Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, Laboratório de Bioquímica de Proteínas e Peptídeos, 21040-360, Rio de Janeiro, RJ, Brazil. Electronic address: floriano@ioc.fiocruz.br.
authors: Floriano Paes
authors: FP
authors: Silva
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020014:K562 Cells; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000473:pathology*; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000473:pathology*; D015394:Molecular Structure; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D005663:Furans; D009285:Naphthoquinones; D014230:Triazoles
keywords: 1,2,3-Triazole; Cancer; Cytotoxic activity; Leukemia; Naphthoquinone; Organic synthesis