Isothiocoumarin-3-carboxylic acid derivatives: synthesis, anticancer and antitrypanosomal activity evaluation

Danylo Kaminskyy; Anna Kryshchyshyn; Ihor Nektegayev; Olexandr Vasylenko; Philippe Grellier; Roman Lesyk

doi:10.1016/j.ejmech.2014.01.028

Isothiocoumarin-3-carboxylic acid derivatives: synthesis, anticancer and antitrypanosomal activity evaluation

Eur J Med Chem. 2014 Mar 21:75:57-66. doi: 10.1016/j.ejmech.2014.01.028. Epub 2014 Jan 25.

Authors

Danylo Kaminskyy¹, Anna Kryshchyshyn¹, Ihor Nektegayev¹, Olexandr Vasylenko², Philippe Grellier³, Roman Lesyk⁴

Affiliations

¹ Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv 79010, Ukraine.
² Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, Murmanska 1, Kyiv 02094, Ukraine.
³ National Museum of Natural History, UMR 7245 CNRS-MNHN, Team APE, CP 52, 57 Rue Cuvier, 75005 Paris, France.
⁴ Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, Lviv 79010, Ukraine. Electronic address: dr_r_lesyk@org.lviv.net.

PMID: 24530491
DOI: 10.1016/j.ejmech.2014.01.028

Abstract

A series of new isothiocoumarin-3-carboxylic acids derivatives had been obtained based on the 5-arylidenerhodanines hydrolysis. Anticancer activity screening allowed identification of 7,8-dimethoxy-1-oxo-1H-isothiochromene-3-carboxylic acid (4-phenylthiazol-2-yl)-amide (30) with the highest level of antimitotic activity (GI50NCI-H322M/NSC Lung Cancer = 1.28 μM). Evaluation of the antitrypanosomal activity against Trypanosoma brucei brucei showed that investigated compounds did not exhibit significant antiparasitic effects. Additionally, the most pharmacologically attractive compounds were non-toxic and well tolerated by the experimental animals.

Keywords: 5-Ylidenerhodanines; Anticancer activity; Antitrypanosomal activity; Isothiocoumarins; Synthesis.

MeSH terms

Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology
Carboxylic Acids / chemical synthesis
Carboxylic Acids / chemistry*
Carboxylic Acids / pharmacology
Cell Line, Tumor
Coumarins / chemical synthesis
Coumarins / chemistry*
Coumarins / pharmacology
Drug Screening Assays, Antitumor
Humans
Neoplasms / drug therapy
Parasitic Sensitivity Tests
Trypanocidal Agents / chemical synthesis
Trypanocidal Agents / chemistry*
Trypanocidal Agents / pharmacology
Trypanosoma brucei brucei / drug effects*
Trypanosomiasis / drug therapy

Substances

Antineoplastic Agents
Carboxylic Acids
Coumarins
Trypanocidal Agents