2. Academic Validation
  3. Molecular design, synthesis and anticancer activity of new thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone)

Molecular design, synthesis and anticancer activity of new thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone)

  • Eur J Med Chem. 2023 Apr 5;252:115304. doi: 10.1016/j.ejmech.2023.115304.
Iryna Ivasechko 1,  Andrii Lozynskyi 2,  Julia Senkiv 1,  Piotr Roszczenko 3,  Yuliia Kozak 1,  Nataliya Finiuk 1,  Olga Klyuchivska 1,  Nataliya Kashchak 1,  Nazar Manko 1,  Zvenyslava Maslyak 4,  Danylo Lesyk 2,  Andriy Karkhut 5,  Svyatoslav Polovkovych 5,  Robert Czarnomysy 6,  Olga Szewczyk 6,  Andriy Kozytskiy 7,  Olexandr Karpenko 8,  Dmytro Khyluk 9,  Andrzej Gzella 10,  Krzysztof Bielawski 6,  Anna Bielawska 3,  Petr Dzubak 11,  Sona Gurska 11,  Marian Hajduch 11,  Rostyslav Stoika 12,  Roman Lesyk 13
Affiliations

Affiliations

  • 1 Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov14/16, Lviv, 79005, Ukraine.
  • 2 Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine.
  • 3 Department of Biotechnology, Faculty of Pharmacy, Medical University of Bialystok, Jana Kilińskiego 1, 15-089, Bialystok, Poland.
  • 4 Institute of Blood Pathology and Transfusion Medicine of National Academy of Medical Sciences of Ukraine, General Chuprynky 45, Lviv, 79044, Ukraine.
  • 5 Department of Technology of Biologically Active Substances, Pharmacy and Biotechnology, Lviv Polytechnic National University, Bandera 12, Lviv, 79013, Ukraine.
  • 6 Department of Synthesis and Technology of Drugs, Faculty of Pharmacy, Medical University of Bialystok, Jana Kilińskiego 1, 15-089, Bialystok, Poland.
  • 7 Enamine Ltd, Chervonotkatska Street 78, Kyiv, 02094, Ukraine; L.V. Pysarzhevsky Institute of Physical Chemistry, National Academy of Sciences of Ukraine, Nauky Avenue 31, Kyiv, 03028, Ukraine.
  • 8 Enamine Ltd, Chervonotkatska Street 78, Kyiv, 02094, Ukraine.
  • 9 Department of Organic Chemistry, Faculty of Pharmacy with Medical Analytics Division, Medical University of Lublin, 4A Chodzki, Lublin, 20-093, Poland.
  • 10 Department of Organic Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6, 60-780, Poznan, Poland.
  • 11 Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University and University Hospital in Olomouc, Hnevotinska 5, 77900, Olomouc, Czech Republic.
  • 12 Institute of Cell Biology of National Academy of Sciences of Ukraine, Drahomanov14/16, Lviv, 79005, Ukraine. Electronic address: [email protected].
  • 13 Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv, 79010, Ukraine; Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225, Rzeszow, Poland. Electronic address: [email protected].
PMID: 37001390 DOI: 10.1016/j.ejmech.2023.115304
Abstract

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.

Keywords

Anticancer activity; Apoptosis; DNA interaction; Drug design; Juglone; Molecular docking; Thiopyranothiazoles.

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