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Open AccessArticle

2,4-Dichlorophenoxyacetic Thiosemicarbazides as a New Class of Compounds Against Stomach Cancer Potentially Intercalating with DNA

1
Independent Radiopharmacy Unit, Department of Organic Chemistry, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland
2
Independent Medical Biology Unit, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland
3
Student research group, Independent Radiopharmacy Unit, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland
4
Department of Synthesis and Chemical Technology of Pharmaceutical Substances, Faculty of Pharmacy, Medical University of Lublin, PL-20093 Lublin, Poland
5
School of Pharmacy, University of Eastern Finland, Yliopistonranta 1, P.O. Box 1627, FI-70211 Kuopio, Finland
*
Author to whom correspondence should be addressed.
This work was partially presented at the 11th Joint Meeting on Medicinal Chemistry 2019, Prague, Czech, 27–30, June 2019, P-70.
Biomolecules 2020, 10(2), 296; https://doi.org/10.3390/biom10020296 (registering DOI)
Received: 14 December 2019 / Revised: 7 February 2020 / Accepted: 11 February 2020 / Published: 13 February 2020
hiosemicarbazide is a useful structural moiety that has the biological potential. Optimization of this structure can result in groundbreaking discovery of a new class of therapeutic agents. In the light of this, 1-(2,4-dichlorophenoxy)acetyl-4-(1-naphthyl)thiosemicarbazide (1) and 1,4-bis[(2,4-dichlorophenoxy)acetylthiosemicarbazide]phenyl (2) were synthesized and characterized by spectroscopic method. Cytotoxicity of obtained compounds was evaluated on MKN74 gastric cancer cell line and human skin fibroblast BJ based on methylthiazolyldiphenyl-tetrazolium bromide (MTT) test. The apoptosis/necrosis and cell cycle analysis were conducted using image cytometry. Additionally, in DNA of treated cells, abasic sites (AP) and double strands breaks (DSB) presence were measured. Intercalating properties of active compounds were evaluated using the UV–spectroscopic method. Among newly synthesized derivatives, compound 2 showed toxic effects on gastric cancer cells with simultaneous lack of toxicity to normal fibroblasts. Cell cycle analysis revealed that both compounds influence cell division mainly at the stage of replication. Simultaneously with DNA synthesis disorders, DNA damages like AP-sites and DSBs were observed. Spectroscopic studies revealed possible DNA intercalating properties of tested compounds. Obtained results indicate that the newly synthesized thiosemicarbazide derivatives are a promising group of compounds with potential anticancer activity resulted from interactions with DNA and cell cycle interrupt.
Keywords: thiosemicarbazide; cytotoxicity; cell cycle; DNA; DNA intercalators thiosemicarbazide; cytotoxicity; cell cycle; DNA; DNA intercalators
MDPI and ACS Style

Pitucha, M.; Korga-Plewko, A.; Kozyra, P.; Iwan, M.; Kaczor, A.A. 2,4-Dichlorophenoxyacetic Thiosemicarbazides as a New Class of Compounds Against Stomach Cancer Potentially Intercalating with DNA. Biomolecules 2020, 10, 296.

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