Journal of Medicinal Chemistry, volume 41, issue 12, pages 2056-2067
Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent
1
Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Company, Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka-ken 411-8731, Japan
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Publication type: Journal Article
Publication date: 1998-05-08
Journal:
Journal of Medicinal Chemistry
Quartile SCImago
Q1
Quartile WOS
Q1
Impact factor: 7.3
ISSN: 00222623, 15204804
Drug Discovery
Molecular Medicine
Abstract
Recently, we reported that 5,4'-diamino-6,8,3'-trifluoroflavone (1b) exhibits potent antitumor activity against certain types of human cancer cell lines both in vitro and in vivo. Since the antiproliferative activity of 5,4'-diaminoflavone (1a), the lead compound of 1b, was modulated by the addition of apigenin, we hypothesized that the 7-position is important for the interaction with a putative target molecule. On the basis of this hypothesis, the structure-activity relationships of the substituents at the 7-position of 1b were explored. As a result, 7-methyl (7a), 7-hydroxymethyl (7l), 7-(acyloxy)methyl (9a,c,e,g,j), and 7-aminomethyl (12f) derivatives were found to exhibit comparable or superior antitumor activity to compound 1b against MCF-7 cells both in vitro and in vivo (po administration). In particular, compounds 9e,g,j, and 12f were sufficiently water-soluble as compared with 1b which hardly solubilizes in water. A lipophilic 7-(hexanoyloxy)methyl derivative (9c) was also found to exhibit strong antitumor activity especially in vivo. Since the modes of action and the target molecule(s) are unknown, a mechanistic study will be important in the future.
Top-30
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1 publication, 3.13%
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1 publication, 3.13%
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1 publication, 3.13%
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1 publication, 3.13%
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1 publication, 3.13%
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Citations by publishers
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Elsevier
8 publications, 25%
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Wiley
6 publications, 18.75%
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American Association for Cancer Research (AACR)
4 publications, 12.5%
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American Chemical Society (ACS)
3 publications, 9.38%
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American Society for Pharmacology and Experimental Therapeutics
2 publications, 6.25%
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Springer Nature
2 publications, 6.25%
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Taylor & Francis
2 publications, 6.25%
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Thieme
2 publications, 6.25%
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Multidisciplinary Digital Publishing Institute (MDPI)
1 publication, 3.13%
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Taras Shevchenko National University of Kyiv
1 publication, 3.13%
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Autonomous Non-profit Organization Editorial Board of the journal Uspekhi Khimii
1 publication, 3.13%
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- We do not take into account publications 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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Akama T. et al. Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent // Journal of Medicinal Chemistry. 1998. Vol. 41. No. 12. pp. 2056-2067.
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Akama T., Ishida H., Kimura U., Gomi K., Saito H. Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent // Journal of Medicinal Chemistry. 1998. Vol. 41. No. 12. pp. 2056-2067.
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TY - JOUR
DO - 10.1021/jm970728z
UR - https://doi.org/10.1021/jm970728z
TI - Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent
T2 - Journal of Medicinal Chemistry
AU - Akama, Tsutomu
AU - Ishida, Hiroyuki
AU - Kimura, Uichiro
AU - Gomi, Katsushige
AU - Saito, Hiromitsu
PY - 1998
DA - 1998/05/08 00:00:00
PB - American Chemical Society (ACS)
SP - 2056-2067
IS - 12
VL - 41
SN - 0022-2623
SN - 1520-4804
ER -
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@article{1998_Akama,
author = {Tsutomu Akama and Hiroyuki Ishida and Uichiro Kimura and Katsushige Gomi and Hiromitsu Saito},
title = {Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent},
journal = {Journal of Medicinal Chemistry},
year = {1998},
volume = {41},
publisher = {American Chemical Society (ACS)},
month = {may},
url = {https://doi.org/10.1021/jm970728z},
number = {12},
pages = {2056--2067},
doi = {10.1021/jm970728z}
}
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Akama, Tsutomu, et al. “Structure−Activity Relationships of the 7-Substituents of 5,4‘-Diamino-6,8,3‘-trifluoroflavone, a Potent Antitumor Agent.” Journal of Medicinal Chemistry, vol. 41, no. 12, May. 1998, pp. 2056-2067. https://doi.org/10.1021/jm970728z.