Anti-liver cancer activity in vitro and in vivo induced by 2-pyridyl 2,3-thiazole derivatives

A total of 24 hybrid compounds containing pyridyl and 1,3-thiazole moieties were screened against HL-60 (leukemia), MCF-7 (breast adenocarcinoma), HepG2 (hepatocellular carcinoma), NCI-H292 (lung carcinoma) human tumor cell lines and non-tumor cells (PBMC, human peripheral blood mononuclear cells)....

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Bibliographic Details
Published in:Toxicology and applied pharmacology 2017-08, Vol.329, p.212-223
Main Authors: dos Santos Silva, Thiago David, Bomfim, Larissa Mendes, da Cruz Rodrigues, Ana Carolina Borges, Dias, Rosane Borges, Sales, Caroline Brandi Schlaepfer, Rocha, Clarissa Araújo Gurgel, Soares, Milena Botelho Pereira, Bezerra, Daniel Pereira, de Oliveira Cardoso, Marcos Veríssimo, Leite, Ana Cristina Lima, Militão, Gardenia Carmen Gadelha
Format: Article
Language:English
Subjects:
2-Pyridyl 2,3-thiazoles
60 APPLIED LIFE SCIENCES
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - toxicity
Antitumor
APOPTOSIS
Apoptosis - drug effects
AZOLES
Cell Proliferation - drug effects
Cell Survival - drug effects
Cytotoxicity
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm
Female
Hep G2 Cells
HepG2
HL-60 Cells
Humans
IN VIVO
Inhibitory Concentration 50
Liver Cancer
Liver Neoplasms - drug therapy
Liver Neoplasms - pathology
MAMMARY GLANDS
MCF-7 Cells
Mice, SCID
Necrosis
Pyridines - pharmacology
Pyridines - toxicity
Thiazoles - pharmacology
Thiazoles - toxicity
TOXICITY
Tumor Burden - drug effects
TUMOR CELLS
Xenograft Model Antitumor Assays
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Summary:A total of 24 hybrid compounds containing pyridyl and 1,3-thiazole moieties were screened against HL-60 (leukemia), MCF-7 (breast adenocarcinoma), HepG2 (hepatocellular carcinoma), NCI-H292 (lung carcinoma) human tumor cell lines and non-tumor cells (PBMC, human peripheral blood mononuclear cells). Most of them were highly potent in at least one cell line tested (IC50≤3μM), being HL-60 the most sensitive and HepG2 the most resistant cell line. Among them, TAP-07 and TP-07 presented cytotoxic activity in all tumor cell lines, including HepG2 (IC50 2.2 and 5.6μM, respectively) without antiproliferative effects to normal cells (PBMC) (IC50>30μM), making TAP-07 and TP-07, the compounds with the most favorable selectivity index. TAP-07 and TP-07 induced apoptosis in HepG2 cells and presented in vivo antitumor activity in hepatocellular xenograft cancer model in C.B-17 severe combined immunodeficient mice. Systemic toxicological verified by biochemical and histopathological techniques reveled no major signs of toxicity after treatment with TAP-07 and TP-07. Together the results indicated the anti-liver cancer activity of 2-pyridyl 2,3-thiazole derivatives. •2-Pyridyl 2,3-thiazole derivatives induce selective cytotoxicity to cancer cell lines.•2-Pyridyl 2,3-thiazole derivatives cause cell death by apoptosis in HepG2 cells.•2-Pyridyl 2,3-thiazole derivatives inhibit the progression of xenograft HepG2 liver cancer in SCID mice.•2-Pyridyl 2,3-thiazole derivatives present no major signs of toxicity.
ISSN:0041-008X
1096-0333
DOI:10.1016/j.taap.2017.06.003