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. 2019 Dec 25;25(1):88.
doi: 10.3390/molecules25010088.

The N'-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity

Izabela Jęśkowiak  1 , Stanisław Ryng  1 , Marta Świtalska  2 , Joanna Wietrzyk  2 , Iwona Bryndal  3 , Tadeusz Lis  4 , Marcin Mączyński  1
Affiliations

The N'-Substituted Derivatives of 5-Chloro-3-Methylisothiazole-4-Carboxylic Acid Hydrazide with Antiproliferative Activity

Izabela Jęśkowiak et al. Molecules. .

Abstract

Thanks to the progress in oncology, pharmacological treatment of cancer is gaining in importance and in the near future anti-cancer chemotherapeutics are expected to be the main method of treatment for cancer diseases. What is more, the search for new anti-cancer compounds with the desired application properties is constantly underway. As a result of designed syntheses, we obtained some new N'-substituted 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives with anticancer activity. The structure of new compounds was determined by mass spectrometry (MS), elemental analysis, proton nuclear magnetic resonance spectroscopy (1H-NMR), carbon nuclear magnetic resonance spectroscopy (13C-NMR), 1H-13C NMR correlations and infrared spectroscopy (IR). Moreover, the structures of the compounds were confirmed by crystallographic examination. The antiproliferative MTT tests for 11 prepared compounds was conducted towards human biphenotypic B cell myelomonocytic leukemia MV4-11. SRB test was used to examine their potential anticancer activity towards human colon adenocarcinoma cell lines sensitive LoVo, resistant to doxorubicin LoVo/DX, breast adenocarcinoma MCF-7 and normal non-tumorigenic epithelial cell line derived from mammary gland MCF-10A. The most active compound was 5-chloro-3-methyl-N'-[(1E,2E)-(3-phenyloprop-2-en-1-ylidene]isothiazole-4-carbohydrazide, which showed the highest antiproliferative activity against all tested cell lines.

Keywords: 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives; antiproliferative activity; isothiazole.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Scheme 1
Scheme 1
Synthesis of 5-chloro-3-methylizothiazole-4-carboxylic acid hydrazide derivatives.
Figure 1
Figure 1
The correlation spectrum of proton and carbon of the most active compound 3 from this series.
Figure 2
Figure 2
X-ray structures of 3 (a) (the dotted line indicates N-H…O hydrogen bond which linking together both independent molecules—denoted as A and B), 4 (b) and 8 (c), with atom-numbering scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radii. For compounds 2 and 3, atoms and bonds from a disordered isothiazole ring with a lower occupancy factor were marked with a transparency of 0.6.
See this image and copyright information in PMC

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