Archiv der Pharmazie, volume 355, issue 5, pages 2100425
Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.
Sadovnikov Kirill S
1
,
Gracheva Yulia A.
1
,
Zefirov Nikolay A
1
,
Palyulin V. A.
1
,
Grishin Yuri
1
,
Vasilichin Vladislav A
1
,
Shtil Alexander A.
1, 2
,
Shevtsov P. N.
3
,
Shevtsova E. F.
3
,
Kuznetsova Tamara S.
1
,
Kuznetsov Sergei A.
4
,
Zefirova Olga N
1
,
R. Milaeva Elena
1
,
4
Institute of Biological Sciences, Cell Biology and Biosystems Technology University of Rostock Rostock Germany
|
Publication type: Journal Article
Publication date: 2022-02-01
Journal:
Archiv der Pharmazie
Quartile SCImago
Q2
Quartile WOS
Q1
Impact factor: 5.1
ISSN: 03656233, 15214184
Drug Discovery
Pharmaceutical Science
Abstract
A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin‐targeting lead molecules with the acylated 4‐aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β‐aryl‐substituted vinylketones by tert‐butyl nitrite in the presence of water as a key step. 4‐Methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 µM and to totally inhibit cell growth (IC50 = 0.99 µM) and cell viability (IC50 = 0.271 µM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5‐trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3‐methyl‐N‐[5‐methyl‐3‐(3,4,5‐trimethoxyphenyl)isoxazol‐4‐yl]benzamide (1ab) to the androgen‐sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 µM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI‐26 VA4 (IC50 = 2.26 µM) and human umbilical vein endothelial cells (IC50 = 5.58 µM) and significantly higher than that to primary fibroblasts (IC50 > 75 µM).
Citations by journals
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1
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1 publication, 16.67%
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Asian Journal of Organic Chemistry
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ChemistrySelect
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Russian Chemical Bulletin
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1 publication, 16.67%
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1
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Citations by publishers
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1
2
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Wiley
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Wiley
2 publications, 33.33%
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Multidisciplinary Digital Publishing Institute (MDPI)
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2 publications, 33.33%
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Elsevier
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1 publication, 16.67%
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Springer Nature
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Springer Nature
1 publication, 16.67%
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1
2
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- We do not take into account publications that without a DOI.
- Statistics recalculated only for publications connected to researchers, organizations and labs registered on the platform.
- Statistics recalculated weekly.
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Sadovnikov K. S. et al. Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells. // Archiv der Pharmazie. 2022. Vol. 355. No. 5. p. 2100425.
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Sadovnikov K. S., Vasilenko D. A., Gracheva Y. A., Zefirov N. A., Radchenko E. V., Palyulin V. A., Grishin Y., Vasilichin V. A., Shtil A. A., Shevtsov P. N., Shevtsova E. F., Kuznetsova T. S., Kuznetsov S. A., Bunev A. S., Zefirova O. N., R. Milaeva E., Averina E. B. Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells. // Archiv der Pharmazie. 2022. Vol. 355. No. 5. p. 2100425.
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TY - JOUR
DO - 10.1002/ardp.202100425
UR - https://doi.org/10.1002%2Fardp.202100425
TI - Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.
T2 - Archiv der Pharmazie
AU - Vasilenko, Dmitry A.
AU - Gracheva, Yulia A.
AU - Vasilichin, Vladislav A
AU - Kuznetsova, Tamara S.
AU - Kuznetsov, Sergei A.
AU - Sadovnikov, Kirill S
AU - Zefirov, Nikolay A
AU - Zefirova, Olga N
AU - Shtil, Alexander A.
AU - Bunev, Alexander S.
AU - Averina, E. B.
AU - Radchenko, Eugene V.
AU - Palyulin, V. A.
AU - Grishin, Yuri
AU - Shevtsov, P. N.
AU - Shevtsova, E. F.
AU - R. Milaeva, Elena
PY - 2022
DA - 2022/02/01 00:00:00
PB - Wiley
SP - 2100425
IS - 5
VL - 355
SN - 0365-6233
SN - 1521-4184
ER -
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@article{2022_Sadovnikov,
author = {Dmitry A. Vasilenko and Yulia A. Gracheva and Vladislav A Vasilichin and Tamara S. Kuznetsova and Sergei A. Kuznetsov and Kirill S Sadovnikov and Nikolay A Zefirov and Olga N Zefirova and Alexander A. Shtil and Alexander S. Bunev and E. B. Averina and Eugene V. Radchenko and V. A. Palyulin and Yuri Grishin and P. N. Shevtsov and E. F. Shevtsova and Elena R. Milaeva},
title = {Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells.},
journal = {Archiv der Pharmazie},
year = {2022},
volume = {355},
publisher = {Wiley},
month = {feb},
url = {https://doi.org/10.1002%2Fardp.202100425},
number = {5},
pages = {2100425},
doi = {10.1002/ardp.202100425}
}
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Sadovnikov, Kirill S., et al. “Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells..” Archiv der Pharmazie, vol. 355, no. 5, Feb. 2022, p. 2100425. https://doi.org/10.1002%2Fardp.202100425.