cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays

cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays Full article

Journal

Journal of Natural Products
ISSN: 0163-3864 , E-ISSN: 1520-6025

Output data

Year: 2013, Volume: 76, Number: 8, Pages: 1485-1491 Pages count : 7 DOI: 10.1021/np400310m

Authors

Tsyganov Dmitry V. ¹ , Konyushkin Leonid D. ¹ , Karmanova Irina B. ¹ , Firgang Sergei I. ¹ , Strelenko Yuri A. ¹ , Semenova Marina N. ^2,3 , Kiselyov Alex S. ⁴ , Semenov Victor V. ¹

Affiliations

1	N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prospect, 47, 119991, Moscow, Russian Federation
2	Chemical Block Ltd., 3 Kyriacou Matsi, 3723 Limassol, Cyprus
3	Institute of Developmental Biology, RAS, Vavilov Street, 26, 119334, Moscow, Russian Federation
4	ChemDiv, Inc., 6605 Nancy Ridge Drive, San Diego, California 92121, United States

We have synthesized a series of novel cis-restricted 4,5-polyalkoxydiaryl-3-aminopyrazole analogues of combretastatins via short synthetic sequences using building blocks isolated from dill and parsley seed extracts. The resulting compounds were tested in vivo in the phenotypic sea urchin embryo assay to reveal their antimitotic and antitubulin effects. The most potent aminopyrazole, 14a, altered embryonic cell division at 10 nM concentration, exhibiting microtubule-destabilizing properties. Compounds 12a and 14a displayed pronounced cytotoxicity in the NCI60 anticancer drug screen, with the ability to inhibit growth of multi-drug-resistant cancer cells.

Tsyganov D.V. , Konyushkin L.D. , Karmanova I.B. , Firgang S.I. , Strelenko Y.A. , Semenova M.N. , Kiselyov A.S. , Semenov V.V.
cis-Restricted 3-Aminopyrazole Analogues of Combretastatins: Synthesis from Plant Polyalkoxybenzenes and Biological Evaluation in the Cytotoxicity and Phenotypic Sea Urchin Embryo Assays
Journal of Natural Products. 2013. V.76. N8. P.1485-1491. DOI: 10.1021/np400310m WOS Scopus OpenAlex

Web of science:	WOS:000323630500013
Scopus:	2-s2.0-84883138617
OpenAlex:	W2318111435

DB	Citing
OpenAlex	41
Web of science	37
Scopus	39