Research output: Contribution to journal › Article › peer-review
1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents. / Sirazhetdinova, Nafisa S.; Savelyev, Victor A.; Frolova, Tatyana S. et al.
In: Molecules (Basel, Switzerland), Vol. 25, No. 11, 2547, 06.2020.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - 1-Hydroxyanthraquinones Containing Aryl Substituents as Potent and Selective Anticancer Agents
AU - Sirazhetdinova, Nafisa S.
AU - Savelyev, Victor A.
AU - Frolova, Tatyana S.
AU - Baev, Dmitry S.
AU - Klimenko, Lyubov S.
AU - Chernikov, Ivan V.
AU - Oleshko, Olga S.
AU - Sarojan, Teresa A.
AU - Pokrovskii, Andrey G.
AU - Shults, Elvira E.
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - A series of 1,2-, 1,4-disubstituted or 1,2,4-trisubstituted anthraquinone-based compounds was designed, synthesized, characterized and biologically evaluated for anticancer efficacy. 2- or 4-arylated 1-hydroxy-9,10-antraquinones (anthracene-9,10-diones) were prepared by Suzuki-Miyaura cross-coupling reaction of 1-hydroxy-2-bromoanthraquinone, 1-hydroxy-4-iodoanthraquinone or 1-hydroxy-2,4-dibromoanthraquinone with arylboronic acids. The cross-coupling reaction of 2,4-dibromo-9,10-anthraquinone with arylboronic acids provide a convenient approach to 2,4-bis arylated 1-hydroxyanthraquinones with a variety of aryl substituent in the 2 and 4 position. The cytotoxicity of new anthraquinone derivatives was evaluated using the conventional MTT assays. The data revealed that six of the aryl substituted compounds among the entire series 3, 15, 16, 25, 27, 28 were comparable potent with the commercially available reference drug doxorubicin on the human glioblastoma cells SNB-19, prostate cancer DU-145 or breast cancer cells MDA-MB-231 and were relatively safe towards human telomerase (h-TERT)immortalized lung fibroblasts cells. The results suggested that the in vitro antitumor activity of synthesized 2-aryl, 4-aryl- and 2,4-diaryl substituted 1-hydroxyanthraquinones depends on the nature of the substituent within the cyclic backbone. Docking interaction of 2-, 4-substituted and 2,4-disubstituted 1-hydroxyanthraquinones indicates intercalative mode of binding of compounds with DNA topoisomerase. The interaction with the DNA of 4-aryl-13, 15, 16 and 4-(furan-3-yl)-23 1-hydroxyanthraquinones was experimentally confirmed through a change in electroforetic mobility. Further experiments with 1-hydroxy-4-phenyl-anthraquinone 13 demonstrated that the compound induced cell cycle arrest at sub-G1 phase in DU-145 cells in the concentration 1.1 μM, which is probably achieved by inducing apoptosis. 4-Arylsubstituted 1-hydroxyanthraquinones 13 and 16 induced the enhancement of DNA synthesis on SNB19 cell lines.
AB - A series of 1,2-, 1,4-disubstituted or 1,2,4-trisubstituted anthraquinone-based compounds was designed, synthesized, characterized and biologically evaluated for anticancer efficacy. 2- or 4-arylated 1-hydroxy-9,10-antraquinones (anthracene-9,10-diones) were prepared by Suzuki-Miyaura cross-coupling reaction of 1-hydroxy-2-bromoanthraquinone, 1-hydroxy-4-iodoanthraquinone or 1-hydroxy-2,4-dibromoanthraquinone with arylboronic acids. The cross-coupling reaction of 2,4-dibromo-9,10-anthraquinone with arylboronic acids provide a convenient approach to 2,4-bis arylated 1-hydroxyanthraquinones with a variety of aryl substituent in the 2 and 4 position. The cytotoxicity of new anthraquinone derivatives was evaluated using the conventional MTT assays. The data revealed that six of the aryl substituted compounds among the entire series 3, 15, 16, 25, 27, 28 were comparable potent with the commercially available reference drug doxorubicin on the human glioblastoma cells SNB-19, prostate cancer DU-145 or breast cancer cells MDA-MB-231 and were relatively safe towards human telomerase (h-TERT)immortalized lung fibroblasts cells. The results suggested that the in vitro antitumor activity of synthesized 2-aryl, 4-aryl- and 2,4-diaryl substituted 1-hydroxyanthraquinones depends on the nature of the substituent within the cyclic backbone. Docking interaction of 2-, 4-substituted and 2,4-disubstituted 1-hydroxyanthraquinones indicates intercalative mode of binding of compounds with DNA topoisomerase. The interaction with the DNA of 4-aryl-13, 15, 16 and 4-(furan-3-yl)-23 1-hydroxyanthraquinones was experimentally confirmed through a change in electroforetic mobility. Further experiments with 1-hydroxy-4-phenyl-anthraquinone 13 demonstrated that the compound induced cell cycle arrest at sub-G1 phase in DU-145 cells in the concentration 1.1 μM, which is probably achieved by inducing apoptosis. 4-Arylsubstituted 1-hydroxyanthraquinones 13 and 16 induced the enhancement of DNA synthesis on SNB19 cell lines.
KW - anthraquinones
KW - cytotoxicity
KW - DNA binding
KW - Suzuki cross-coupling reaction
KW - DESIGN
KW - MITOXANTRONE
KW - ANTHRAQUINONE DERIVATIVES
KW - PROLIFERATION
KW - KNIPHOLONE
KW - INHIBITORS
KW - CANCER
KW - MOLECULES
KW - Cytotoxicity
KW - Anthraquinones
KW - Humans
KW - Telomerase/metabolism
KW - Structure-Activity Relationship
KW - Antineoplastic Agents/pharmacology
KW - Drug Design
KW - Molecular Structure
KW - Cell Proliferation/drug effects
KW - Magnetic Resonance Spectroscopy
KW - Anthraquinones/chemical synthesis
KW - DNA/chemistry
KW - Cell Line, Tumor
KW - Molecular Docking Simulation
KW - Apoptosis
KW - Drug Screening Assays, Antitumor
UR - http://www.scopus.com/inward/record.url?scp=85085909526&partnerID=8YFLogxK
U2 - 10.3390/molecules25112547
DO - 10.3390/molecules25112547
M3 - Article
C2 - 32486108
AN - SCOPUS:85085909526
VL - 25
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 11
M1 - 2547
ER -
ID: 24518377