Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments

Standard

Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments. / Popova, Elena A.; Ovsepyan, Gayane K.; Protas, Aleksandra V.; Erkhitueva, Elena B.; Kukhanova, Marina K.; Yesaulkova, Yana L.; Zarubaev, Vladimir V.; Starova, Galina L.; Suezov, Roman V.; Eremin, Alexei V.; Ostrovskii, Vladimir A.; Trifonov, Rostislav E.

In: Nucleosides, Nucleotides and Nucleic Acids, Vol. 38, No. 10, 03.10.2019, p. 713-731.

Research output: Contribution to journal › Article › peer-review

Author

Popova, Elena A. ; Ovsepyan, Gayane K. ; Protas, Aleksandra V. ; Erkhitueva, Elena B. ; Kukhanova, Marina K. ; Yesaulkova, Yana L. ; Zarubaev, Vladimir V. ; Starova, Galina L. ; Suezov, Roman V. ; Eremin, Alexei V. ; Ostrovskii, Vladimir A. ; Trifonov, Rostislav E. / Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments. In: Nucleosides, Nucleotides and Nucleic Acids. 2019 ; Vol. 38, No. 10. pp. 713-731.

BibTeX

@article{87ba5835517041fb80068482018569f3,

title = "Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments",

abstract = "3′-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1H- and 2-propargyl-5-R-2H-tetrazoles (R = H, Me, CH2COOEt, CH2CON(CH3)2, Ph, 2-CH3-C6H4, or 4-NO2-C6H4) via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3′-modified thymidine analogs incorporating 1H-1,2,3-triazolyl, 1H-, and 2H-tetrazolyl fragments in 41–76% yield. The structures of the obtained compounds have been elucidated by means of HRESI+-MS, 1H and 13C{1H} NMR, and single crystal X-ray diffraction {for 3′-[4-(1H-5-N,N-dimethylaminocarbonylmethyltetrazol-1-yl)-1H-1,2,3-triazol-1-yl]thymidine 10d}. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1899A. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3′-(4-(1H-tetrazol-1-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 10a (IC50 39.6 μg/mL), 3′-(4-(2H-5-ethoxycarbonyltetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11c (IC50 31.6 μg/mL), and 3′-(4-(2H-5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11g (IC50 46.4 μg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.",

keywords = "1,2,3-triazole, 1D and 2D NMR spectroscopy, anti-influenza and anti-HIV activity, cytotoxicity, single crystal X-ray diffraction, tetrazole, thymidine analogs",

author = "Popova, {Elena A.} and Ovsepyan, {Gayane K.} and Protas, {Aleksandra V.} and Erkhitueva, {Elena B.} and Kukhanova, {Marina K.} and Yesaulkova, {Yana L.} and Zarubaev, {Vladimir V.} and Starova, {Galina L.} and Suezov, {Roman V.} and Eremin, {Alexei V.} and Ostrovskii, {Vladimir A.} and Trifonov, {Rostislav E.}",

note = "Funding Information: This work is supported by the Russian Science Foundation (grant 17-13-01124). Physicochemical measurements were carried out at the Centre for Chemical Analysis and Materials, the Centre for Magnetic Resonance and the X-ray Diffraction Centre (all belong to Saint Petersburg State University). Publisher Copyright: {\textcopyright} 2018, {\textcopyright} 2018 Taylor & Francis Group, LLC. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

year = "2019",

month = oct,

day = "3",

doi = "10.1080/15257770.2018.1541466",

language = "English",

volume = "38",

pages = "713--731",

journal = "Nucleosides and Nucleotides",

issn = "0732-8311",

publisher = "Taylor & Francis",

number = "10",

}

RIS

TY - JOUR

T1 - Synthesis and in vitro Biological Evaluation of Novel Thymidine Analogs Containing 1H-1,2,3-Triazolyl, 1H-Tetrazolyl, and 2H-Tetrazolyl Fragments

AU - Popova, Elena A.

AU - Ovsepyan, Gayane K.

AU - Protas, Aleksandra V.

AU - Erkhitueva, Elena B.

AU - Kukhanova, Marina K.

AU - Yesaulkova, Yana L.

AU - Zarubaev, Vladimir V.

AU - Starova, Galina L.

AU - Suezov, Roman V.

AU - Eremin, Alexei V.

AU - Ostrovskii, Vladimir A.

AU - Trifonov, Rostislav E.

N1 - Funding Information: This work is supported by the Russian Science Foundation (grant 17-13-01124). Physicochemical measurements were carried out at the Centre for Chemical Analysis and Materials, the Centre for Magnetic Resonance and the X-ray Diffraction Centre (all belong to Saint Petersburg State University). Publisher Copyright: © 2018, © 2018 Taylor & Francis Group, LLC. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.

PY - 2019/10/3

Y1 - 2019/10/3

N2 - 3′-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1H- and 2-propargyl-5-R-2H-tetrazoles (R = H, Me, CH2COOEt, CH2CON(CH3)2, Ph, 2-CH3-C6H4, or 4-NO2-C6H4) via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3′-modified thymidine analogs incorporating 1H-1,2,3-triazolyl, 1H-, and 2H-tetrazolyl fragments in 41–76% yield. The structures of the obtained compounds have been elucidated by means of HRESI+-MS, 1H and 13C{1H} NMR, and single crystal X-ray diffraction {for 3′-[4-(1H-5-N,N-dimethylaminocarbonylmethyltetrazol-1-yl)-1H-1,2,3-triazol-1-yl]thymidine 10d}. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1899A. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3′-(4-(1H-tetrazol-1-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 10a (IC50 39.6 μg/mL), 3′-(4-(2H-5-ethoxycarbonyltetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11c (IC50 31.6 μg/mL), and 3′-(4-(2H-5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11g (IC50 46.4 μg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.

AB - 3′-Azidothymidine (AZT) reacts with 1-propargyl-5-R-1H- and 2-propargyl-5-R-2H-tetrazoles (R = H, Me, CH2COOEt, CH2CON(CH3)2, Ph, 2-CH3-C6H4, or 4-NO2-C6H4) via the Cu(I)-catalyzed asymmetric [3 + 2] cycloaddition to give 3′-modified thymidine analogs incorporating 1H-1,2,3-triazolyl, 1H-, and 2H-tetrazolyl fragments in 41–76% yield. The structures of the obtained compounds have been elucidated by means of HRESI+-MS, 1H and 13C{1H} NMR, and single crystal X-ray diffraction {for 3′-[4-(1H-5-N,N-dimethylaminocarbonylmethyltetrazol-1-yl)-1H-1,2,3-triazol-1-yl]thymidine 10d}. In vitro biological evaluation of the prepared compounds has been performed; they have exhibited low activity against phenotypic HIV-1899A. Moderate anti-influenza activity against influenza virus A/Puerto Rico/8/34 (H1N1) strain has been observed in the cases of 3′-(4-(1H-tetrazol-1-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 10a (IC50 39.6 μg/mL), 3′-(4-(2H-5-ethoxycarbonyltetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11c (IC50 31.6 μg/mL), and 3′-(4-(2H-5-(4-nitrophenyl)-tetrazol-2-ylmethyl)-1H-1,2,3-triazol-1-yl)thymidine 11g (IC50 46.4 μg/mL). The tested compounds possess very low cytotoxicity towards MDCK and MT4 cells as well as tumor human cervical carcinoma HeLa and promyelocytic leukemia HL-60 cells.

KW - 1,2,3-triazole

KW - 1D and 2D NMR spectroscopy

KW - anti-influenza and anti-HIV activity

KW - cytotoxicity

KW - single crystal X-ray diffraction

KW - tetrazole

KW - thymidine analogs

UR - http://www.scopus.com/inward/record.url?scp=85064678388&partnerID=8YFLogxK

U2 - 10.1080/15257770.2018.1541466

DO - 10.1080/15257770.2018.1541466

M3 - Article

C2 - 30991893

AN - SCOPUS:85064678388

VL - 38

SP - 713

EP - 731

JO - Nucleosides and Nucleotides

JF - Nucleosides and Nucleotides

SN - 0732-8311

IS - 10

ER -

ID: 35404733