Novel Hybrid Compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide with Antimetastatic and Cytotoxic Action: Synthesis and Anticancer Screening.

Autor:	Zborovskii YL; Institute of Organic Chemistry, NAS of Ukraine, 5 Murmanska St., 02660, Kyiv, Ukraine., Orysyk VV; Institute of Organic Chemistry, NAS of Ukraine, 5 Murmanska St., 02660, Kyiv, Ukraine., Golovynska I; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, 518060, Shenzhen, China., Dzhus OI; Taras Shevchenko National University of Kyiv, ESC 'Institute of Biology and Medicine', 64 Volodymyrska St., 01601, Kyiv, Ukraine., Garmanchuk LV; Taras Shevchenko National University of Kyiv, ESC 'Institute of Biology and Medicine', 64 Volodymyrska St., 01601, Kyiv, Ukraine., Stepanov YV; Taras Shevchenko National University of Kyiv, ESC 'Institute of Biology and Medicine', 64 Volodymyrska St., 01601, Kyiv, Ukraine., Khranovska N; National Cancer Institute, 33/43, Lomonosova Str., 03022, Kyiv, Ukraine., Nehelia AO; Taras Shevchenko National University of Kyiv, ESC 'Institute of Biology and Medicine', 64 Volodymyrska St., 01601, Kyiv, Ukraine., Golovynskyi S; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, 518060, Shenzhen, China., Ohulchanskyy TY; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, 518060, Shenzhen, China., Qu J; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, 518060, Shenzhen, China., Orysyk SI; V.I. Vernadskii Institute of General and Inorganic Chemistry, NAS of Ukraine, 32/34 Palladina Ave., 03680, Kyiv, Ukraine., Pekhnyo VI; V.I. Vernadskii Institute of General and Inorganic Chemistry, NAS of Ukraine, 32/34 Palladina Ave., 03680, Kyiv, Ukraine., Vovk MV; Institute of Organic Chemistry, NAS of Ukraine, 5 Murmanska St., 02660, Kyiv, Ukraine.
Jazyk:	angličtina
Zdroj:	Anti-cancer agents in medicinal chemistry [Anticancer Agents Med Chem] 2018; Vol. 18 (10), pp. 1495-1504.
DOI:	10.2174/1871520618666180313151503
Abstrakt:	Background: One of the most promising strategies to develop multi-targeted anticancer therapeutics is to introduce to the structure of a potential drug two or more pharmacophores (functional groups or structural fragments), which have antiproliferative, proapoptotic or antimetastatic properties acting via different mechanisms. Objective: To design, synthesize and perform screening of a novel hybrid anticancer compound. Method: A novel hybrid compound 4-[(E)-2-phenylethenesulfonamido]-N-hydroxybutanamide, combining butanehydroxamate and styrenesulfonamide moieties, was designed, synthesized and investigated as a potent antimetastatic and antiproliferative agent. The structure and purity of the synthesized compound were confirmed by 1H NMR, 13C NMR, LC/MS spectroscopy and elemental analysis. The compound was screened for the anticancer activity in vitro against HeLa and in vivo against Lewis lung carcinoma tumor, using an antitumor metalloenzyme inhibitor GM6001 (Ilomastat, Galardin) and Pifithrin-μ as control anticancer agents. Results: It was found that the application of our compound resulted in a high fraction of apoptotic cells in the cell population, along with disruption in the cell cycle profile manifested as arrest of proliferative phases. Furthermore, changes of the morphological properties (i.e., an enhancement of adhesive properties and reduction of the nuclear-to-cytoplasm ratio) were found. The in vivo screening revealed that the compound significantly inhibited the metastasizing process that was manifested by a reduction in the number and volume of metastases. Conclusions: The obtained results demonstrate that our compound can serve as a base for further structure optimization in order to design new highly-effective antimetastatic and antitumor agents. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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