TY - JOUR

T1 - Evaluation of antioxidant activity and cytotoxicity of polyfluorinated diarylacetylenes and indoles toward human cancer cells

AU - Zakharova, Olga

AU - Nevinsky, Georgy

AU - Politanskaya, Larisa

AU - Baev, Dmitry

AU - Ovchinnikova, Ludmila

AU - Tretyakov, Evgeny

N1 - Funding Information: The work was supported by RFBR research project ? 19-53-53003. The authors thank the Multi-Access Chemical Service Center SB RAS and Olga Koval for spectral and analytical measurements. Publisher Copyright: © 2019 Elsevier B.V.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - A large series of polyfluorinated diarylacetylenes and indoles was evaluated for antitumor activity in MCF-7, RPMI 8226, T98 G, HCT 116 human cancer cells and for cytotoxicity effect on HEK-293, WI-38, LMTK, AG 17 normal mammalian cell lines. It was found that with the increased number of fluorine atoms on the benzene ring of the compounds, their cytotoxicity increases, reaching a maximum in case of the perfluorinated structures. Polyfluorinated diarylacetylenes containing three fluorine atoms and trifluoromethyl and amino groups in one aryl ring, inhibit the proliferation of human myeloma RPMI 8226 and human breast cancer MCF-7 cells. Indoles showed more pronounced cytotoxicity as compared with their arylacetylene precursors. Compounds I9, I11, and I13 were found to have a high growth-inhibitory activity toward the human cancer cell lines tested, with half-inhibitory concentrations (IC50) of 1–10 μM. The structures of these compounds are characterized by complete fluorination of the benzene part of the indole core and the presence of an aromatic moiety at the 2nd position of the five-membered ring. Further, DNA fragmentation and Annexin V-FITC/PI staining assays confirm that I9 – I11 induce apoptosis. Mutagenic and antioxidant properties of the polyfluorinated indoles and of selected diarylacetylenes were also studied. On a Salmonella tester strain, it was demonstrated that the compounds are good antioxidants.

AB - A large series of polyfluorinated diarylacetylenes and indoles was evaluated for antitumor activity in MCF-7, RPMI 8226, T98 G, HCT 116 human cancer cells and for cytotoxicity effect on HEK-293, WI-38, LMTK, AG 17 normal mammalian cell lines. It was found that with the increased number of fluorine atoms on the benzene ring of the compounds, their cytotoxicity increases, reaching a maximum in case of the perfluorinated structures. Polyfluorinated diarylacetylenes containing three fluorine atoms and trifluoromethyl and amino groups in one aryl ring, inhibit the proliferation of human myeloma RPMI 8226 and human breast cancer MCF-7 cells. Indoles showed more pronounced cytotoxicity as compared with their arylacetylene precursors. Compounds I9, I11, and I13 were found to have a high growth-inhibitory activity toward the human cancer cell lines tested, with half-inhibitory concentrations (IC50) of 1–10 μM. The structures of these compounds are characterized by complete fluorination of the benzene part of the indole core and the presence of an aromatic moiety at the 2nd position of the five-membered ring. Further, DNA fragmentation and Annexin V-FITC/PI staining assays confirm that I9 – I11 induce apoptosis. Mutagenic and antioxidant properties of the polyfluorinated indoles and of selected diarylacetylenes were also studied. On a Salmonella tester strain, it was demonstrated that the compounds are good antioxidants.

KW - Cytotoxicity

KW - Mutagenic and antioxidant properties

KW - Polyfluorinated 2-arylindoles

KW - Polyfluorinated diarylacetylenes

KW - Structure-activity relationship

KW - TUBULIN POLYMERIZATION

KW - ANTITUMOR-ACTIVITY

KW - POTENT INHIBITORS

KW - GROWTH

KW - CHEMISTRY

KW - FLUORINE

KW - DERIVATIVES

KW - EXPRESSION

UR - http://www.scopus.com/inward/record.url?scp=85069837937&partnerID=8YFLogxK

U2 - 10.1016/j.jfluchem.2019.109353

DO - 10.1016/j.jfluchem.2019.109353

M3 - Article

AN - SCOPUS:85069837937

VL - 226

JO - Journal of Fluorine Chemistry

JF - Journal of Fluorine Chemistry

SN - 0022-1139

M1 - 109353

ER -