Design and Synthesis of 3-(N-Substituted)aminocoumarins as Anticancer Agents from 3-Bromopeuruthenicin

Design and Synthesis of 3-(N-Substituted)aminocoumarins as Anticancer Agents from 3-Bromopeuruthenicin Full article

Journal

ChemistrySelect
ISSN: 2365-6549

Output data

Year: 2019, Volume: 4, Number: 34, Pages: 10197-10201 Pages count : 5 DOI: 10.1002/slct.201901377

Tags

Coumarin; Bromination; Buchwald amination; Suzuki cross-coupling reaction; Cytotoxicity

Authors

Lipeeva Alla, V ¹ , Zakharov Danila O. ^1,2 , Gatilov Yurii, V ^1,2 , Pokrovskii Mikhail A. ² , Pokrovskii Andrey G. ² , Shults Elvira E. ^1,2

Affiliations

1	(Данные Web of science) Novosibirsk Inst Organ Chem, Lab Med Chem, Lavrentyev Ave 9, Novosibirsk 630090, Russia
2	(Данные Web of science) Novosibirsk State Univ, Med Dept, Pirogova St 2, Novosibirsk 630090, Russia

A convenient protocol for the rapid and efficient synthesis of 3-bromopeuruthenicin 2 from plant coumarin peuruthenicin 1 is described. Coumarin 2 have been successfully reacted with N-methylpiperazine, or 5-aminoisoquinoline under reflux in chloroform with the formation of 3-(N-substituted)aminoumbelliferons. The easiness of formation of the mentioned compounds can be explained by occurring of the tautomerization processes in 3-bromo-7-hydroxycoumarin 2 in the reaction conditions. For obtaining high yields of 3-(arylamino)coumarins in the reaction of 3-bromocoumarin 2 with substituted anilines the palladium-catalyzed C-N coupling reaction was studied. The reaction proceeded cleanly in the presence of the Pd(OAc)(2)-Xantphos catalytic system with the formation of the corresponding coupling products. The Suzuki cross-coupling reaction of 3-(3-bromophenylamino)coumarin 8 f with aryl- and (hetaryl)boronic acids 11,13 and 14 using PdCl2(dppf) as the catalyst provided the formation of 3-(N-(aryl-hetaryl))aminocoumarins 12, 15 and 16 in good yields. The cytotoxicity of new umbelliferone derivatives was evaluated against human cancer cells using the conventional MTT assays. The data revealed that compounds 12, 15 and 16 possessed most promising cytotoxic potential; aminocoumarins 12 and 16 shown selectivity toward the breast cancer cells MCF-7. The cytotoxicity of 3-(N-substituted)aminocoumarins 12 and 16 on this cell lines was comparable to those of standard drug Doxorubicin.

Lipeeva A.V. , Zakharov D.O. , Gatilov Y.V. , Pokrovskii M.A. , Pokrovskii A.G. , Shults E.E.
Design and Synthesis of 3-(N-Substituted)aminocoumarins as Anticancer Agents from 3-Bromopeuruthenicin
ChemistrySelect. 2019. V.4. N34. P.10197-10201. DOI: 10.1002/slct.201901377 WOS Scopus РИНЦ OpenAlex

Published print:	Sep 13, 2019
Published online:	Oct 2, 2019

Web of science:	WOS:000490895800045
Scopus:	2-s2.0-85073320795
Elibrary:	10197
OpenAlex:	W2977815008

DB	Citing
Web of science	7
Scopus	7
OpenAlex	6