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

Yurii L Zborovskii; Viktor V Orysyk; Iuliia Golovynska; Olena I Dzhus; Liudmyla V Garmanchuk; Yurii V Stepanov; Natalia Khranovska; Anatolii O Nehelia; Sergii Golovynskyi; Tymish Y Ohulchanskyy; Junle Qu; Svitlana I Orysyk; Vasyl I Pekhnyo; Myhaylo V Vovk

doi:10.2174/1871520618666180313151503

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

Anticancer Agents Med Chem. 2018;18(10):1495-1504. doi: 10.2174/1871520618666180313151503.

Affiliations

¹ Institute of Organic Chemistry, NAS of Ukraine, 5 Murmanska St., 02660, Kyiv, Ukraine.
² Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, 518060, Shenzhen, China.
³ Taras Shevchenko National University of Kyiv, ESC "Institute of Biology and Medicine", 64 Volodymyrska St., 01601, Kyiv, Ukraine.
⁴ National Cancer Institute, 33/43, Lomonosova Str., 03022, Kyiv, Ukraine.
⁵ V.I. Vernadskii Institute of General and Inorganic Chemistry, NAS of Ukraine, 32/34 Palladina Ave., 03680, Kyiv, Ukraine.

PMID: 29532761
DOI: 10.2174/1871520618666180313151503

Abstract

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.

Keywords: Hybrid compound; anticancer; antimetastatic; cytotoxic; hydroxamate; sulfonamide; synthesis..

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design
Drug Evaluation, Preclinical
Drug Screening Assays, Antitumor
Flow Cytometry
HeLa Cells
Humans
Microscopy, Fluorescence
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents