3-(5-)-Amino-o-diarylisoxazoles: Regioselective synthesis and antitubulin activity

3-(5-)-Amino-o-diarylisoxazoles: Regioselective synthesis and antitubulin activity Full article

Journal

European Journal of Medicinal Chemistry
ISSN: 1768-3254 , E-ISSN: 0223-5234

Output data

Year: 2014, Volume: 73, Pages: 112-125 Pages count : 14 DOI: 10.1016/j.ejmech.2013.12.006

Authors

Tsyganov Dmitry V. ¹ , Khrustalev Victor N. ² , Konyushkin Leonid D. ¹ , Raihstat Mikhail M. ^3,1 , Firgang Sergei I. ¹ , Semenov Roman V. ¹ , Kiselyov Alex S. ⁴ , Semenova Marina N. ^3,5 , Semenov Victor V. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry RAS, 47 Leninsky Prospect, 119991 Moscow, Russian Federation
2	A. N. Nesmeyanov Institute of Organoelement Compounds, 28 Vavilov Street, 119991 Moscow, Russian Federation
3	Chemical Block Ltd., 3 Kyriacou Matsi, 3723 Limassol, Cyprus
4	Department of Biological and Medicinal Chemistry, Moscow Institute of Physics and Technology, Institutsky Per. 9, Dolgoprudny, 141700 Moscow Region, Russian Federation
5	N. K. Kol'tsov Institute of Developmental Biology RAS, 26 Vavilov Street, 119334 Moscow, Russian Federation

A regioselective synthesis of both 5-amino- and 3-aminodiarylisoxazoles substituted with polyalkoxyaryl pharmacophores has been validated. Starting materials for the synthetic scheme were easily available from plant extracts. The targeted molecules were further tested in the phenotypic sea urchin embryo assay to identify compounds with antimitotic microtubule destabilizing activity. Structure–activity relationship studies suggested that the structural features essential for potent antiproliferative activity include: 1) 5-aminoisoxazole bridge linking biaryl substituents (rings A and B); 2) unsubstituted 5-amino group; 3) 3,4,5-methoxy substituted benzene and 4-methoxy benzene pharmacophores as rings A and B, respectively. The most potent compounds also showed strong in vitro cytotoxicity in NCI60 anticancer drug screen against a panel of 60 human cancer cell lines, including multi-drug resistant cells.

Tsyganov D.V. , Khrustalev V.N. , Konyushkin L.D. , Raihstat M.M. , Firgang S.I. , Semenov R.V. , Kiselyov A.S. , Semenova M.N. , Semenov V.V.
3-(5-)-Amino-o-diarylisoxazoles: Regioselective synthesis and antitubulin activity
European Journal of Medicinal Chemistry. 2014. V.73. P.112-125. DOI: 10.1016/j.ejmech.2013.12.006 WOS Scopus OpenAlex

Web of science:	WOS:000331916500012
Scopus:	2-s2.0-84891722278
OpenAlex:	W2010261995

DB	Citing
OpenAlex	20
Scopus	19
Web of science	17