Fluoroaryl analogs of sulforaphane - A group of compounds of anticancer and antimicrobial activity.

Autor: Cierpiał T; Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland. Electronic address: tomaszcierpial@yahoo.com., Kiełbasiński P; Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland., Kwiatkowska M; Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland., Łyżwa P; Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland., Lubelska K; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Kuran D; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Dąbrowska A; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Kruszewska H; Department of Antibiotics and Microbiology, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Mielczarek L; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Chilmonczyk Z; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland., Wiktorska K; Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warszawa, Poland. Electronic address: k.wiktorska@nil.gov.pl.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2020 Jan; Vol. 94, pp. 103454. Date of Electronic Publication: 2019 Nov 20.
DOI: 10.1016/j.bioorg.2019.103454
Abstrakt: A series of new sulforaphane analogs bearing various (poly)fluoroaryl substituents bonded to the sulfinyl sulfur atom in place of the original methyl group and having different number of methylene groups in the central alkyl chain were synthesized and fully characterized. The new compounds were tested in vitro for their anticancer, antibacterial, antifungal and antiviral properties. Some of them demonstrated a much higher anticancer activity against selected lines of cancer: skin (MALME-3M), colon (HT-29) and breast (MCF7 and MDA-MB-231) cells than that exhibited by native sulforaphane (SFN). Related lines of untransformed (normal) cells, taken from the same organs as the cancer ones, i.e. MALME3, CRL-1790 and MCF10, respectively, were checked, which allowed for the determination of the selectivity indexes (SI). In certain cases, the latter exceeded 3.2. Concerning the antibacterial activity, gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) were susceptible to some newly synthesized SFN analogs, while the selected probiotic strains were from 10 to 100 fold more resistant to them, which gives a possibility of protection of symbiont strains during a potential therapy with such compounds. The antifungal activity of the new compounds possessing the fluorophenyl substituent was found to be higher than the activity of the parent SFN. In turn, most of the new compounds showed generally no anti-HIV activity. The influence of the particular structural differences in the new molecules, analogs of SFN, on their biological activity is discussed.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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