Fluoroaryl analogs of sulforaphane – A group of compounds of anticancer and antimicrobial activity

• Published in: Bioorganic chemistry 2020-01, Vol.94, p.103454, Article 103454
• Main Authors: Cierpiał, Tomasz, Kiełbasiński, Piotr, Kwiatkowska, Małgorzata, Łyżwa, Piotr, Lubelska, Katarzyna, Kuran, Dominika, Dąbrowska, Aleksandra, Kruszewska, Hanna, Mielczarek, Lidia, Chilmonczyk, Zdzisław, Wiktorska, Katarzyna
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial; Anticancer; Antifungal Agents - chemical synthesis; Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Antifungal and antiviral activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Aspergillus - drug effects; Candida - drug effects; Cell Line; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Isothiocyanates; Isothiocyanates - chemical synthesis; Isothiocyanates - chemistry; Isothiocyanates - pharmacology; Microbial Sensitivity Tests; Molecular Structure; Polyfluoroaryl derivatives; Structure-Activity Relationship; Sulforaphane
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2019.103454

[Display omitted] •A series of new sulforaphane analogs bearing various (poly)fluoroaryl substituents were synthesized and fully characterized.•In vitro tests revealed their enhanced activity against four cancer cell lines.•In vitro investigations showed high activity against gram-positive bacteria and selected fungi.•The antifungal activity was found to be higher than the activity of the parent SFN. 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.