A series of 11-substituted 9-hydroxy-3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones 3.1-3.13 were synthesized via hetero-Diels-Alder reaction of 5-ene-4-thioxo-2-thiazolidinones and 5-hydroxy-1,4-naphthoquinone (juglone). The structure of newly synthesized compounds was established by means of spectral data and a single-crystal X-ray diffraction analysis. The synthesized compounds were tested on a panel of cell lines representing different types of cancer as well as normal and pseudonormal cells and peripheral human blood lymphocytes. Compound 3.10 was found to be the most active derivative, exhibiting a cytotoxic effect similar to doxorubicin's one (IC50 ranged from 0.6 to 5.98 μM), but less toxic to normal and pseudonormal cells. All synthesized compounds were able to interact with DNA, although their anticancer activity did not correlate with the potency of interaction with DNA. The status of p53 in colorectal cancer cells correlated with the activity of the synthesized derivatives 3.1, 3.7, and 3.10. Compound 3.10 did not have an acute toxic effect on the body of С57BL/6 mice, unlike the well-known anticancer drug doxorubicin, which was used as a positive control. The injection of 3.10 (20 mg/kg) to mice had no effect on the counts of leukocytes, erythrocytes, platelets and hemoglobin level in their blood, in contrast to doxorubicin, which caused anemia and leukopenia, indicating bio-tolerance of 3.10in vivo.

Department of Biotechnology and Cell Biology Medical College University of Information Technology and Management in Rzeszow Sucharskiego 2 35 225 Rzeszow Poland

Department of Biotechnology Faculty of Pharmacy Medical University of Bialystok Jana Kilińskiego 1 15 089 Bialystok Poland

Department of Organic Chemistry Faculty of Pharmacy with Medical Analytics Division Medical University of Lublin 4A Chodzki Lublin 20 093 Poland

Department of Organic Chemistry Poznan University of Medical Sciences Grunwaldzka 6 60 780 Poznan Poland

Department of Pharmaceutical Organic and Bioorganic Chemistry Danylo Halytsky Lviv National Medical University Pekarska 69 Lviv 79010 Ukraine

Department of Synthesis and Technology of Drugs Faculty of Pharmacy Medical University of Bialystok Jana Kilińskiego 1 15 089 Bialystok Poland

Department of Technology of Biologically Active Substances Pharmacy and Biotechnology Lviv Polytechnic National University Bandera 12 Lviv 79013 Ukraine

Enamine Ltd Chervonotkatska Street 78 Kyiv 02094 Ukraine

Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine General Chuprynky 45 Lviv 79044 Ukraine

Institute of Cell Biology of National Academy of Sciences of Ukraine Drahomanov14 16 Lviv 79005 Ukraine

Institute of Molecular and Translational Medicine Faculty of Medicine and Dentistry Palacky University and University Hospital in Olomouc Hnevotinska 5 77900 Olomouc Czech Republic

L 5 Pysarzhevsky Institute of Physical Chemistry National Academy of Sciences of Ukraine Nauky Avenue 31 Kyiv 03028 Ukraine

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