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.
Highlights
Chemotherapy is a method of systemic treatment of malignant tumors using cytostatic drugs, which stop the division and spread of cancer cells [1]
5-chloro-3-methylisothiazole-4-carboxylic acid hydrazides with the chlorine substitution of the isothiazole ring in the 5-position. 5-Chloro-3-methyl-isothazole-4-carbohydrazide 2 has already been synthetized by Kuczyński et al [19], whereas in this work we used another method of synthesizing hydrazides through an intermediate azide product (Scheme 1)
The results indicated that the activity of the synthesized derivatives 5-hydrazino-3-methylisothiazole-4-carboxylic acids [29] and new 5-chloro-3-methylisothiazole-4-carboxylic acid hydrazide derivatives 3–11 is mainly associated with the presence of the -N=CH group with a suitable size and shape substituent in
Summary
Chemotherapy is a method of systemic treatment of malignant tumors using cytostatic drugs, which stop the division and spread of cancer cells [1]. The simultaneous administration of several anticancer drugs reduces the risk of developing resistance to the treatment and leads to enhanced cytostatic activity. Molecules 2020, 25, 88 specificity of antitumor drug action of cytostatic agents, their low therapeutic factor and toxicity to normal tissues [2,3,4,5,6], we decided to design new compounds with potential anticancer activity. CP-547.632 39, which belongs to the (3-aryl-4-carboxamido-isothiazol-3-yl)-carbamides, is a promising tyrosine kinase inhibitor with antineoplastic activity [7,8] used in the treatment of non-small cell lung cancer.
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