Synthesis and in vitro evaluation of N-alkyl-3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs as potential anticancer agents

Abstract

A series of novel 3-hydroxy-3-(2-imino-3-methyl-5-oxoimidazolidin-4-yl)indolin-2-one analogs (3) have been synthesized under microwave irradiation and conventional heating methods. These analogs were evaluated for in vitro cytotoxicity against a panel of 57 human tumor cell lines. Compound 3o had GI50 values of 190 nM and 750 nM against A549/ATTC non-small cell lung cancer and LOX IMVI melanoma cell lines, respectively, and both 3n and 3o exhibited GI50 values ranging from 2–5 μM against CCRF-CEM, HL-60(TB), K-562, MOLT-4, and RPMI-8226 leukemia cell lines. These results indicate that N-4-methoxybenzyl-3-hydroxy-(2-imino-3-methyl-5-oxo-4-yl)indolin-2-one analogs may be useful leads for anticancer drug development.

Crystal structure of 1-(4-bromo-2-(2-morpholinoethylamino)phenyl)-2- morpholinoethane-1,2-dione, C18H24BrN3O4

“…1H-indole-2,3-dione derivatives have driven much attention for their bioactivities on anti-HIV [1], anticonvulsant[ 2] and antitumor activities [3,4].Ithas been reported that the introduction of substituents at the Natom of indolin-2-ones enhances their cytotoxicity against avariety of cancer cell lines [5,6]. In an attemptt oo btain compounds that might also exhibit antitumor properties, we carried out the reaction of 6-bromo-1-(2-bromoethyl)indoline-2,3-dione with an excess of morpholine.…”

Crystal structure of 5',7'-dibromo-1'-(2-bromoethyl)spiro[[1,3]dioxolane- 2,3'-indolin]-2'-one, C12H10Br3NO3

“…1H-indole-2,3-dione and its derivatives demonstrate a broad spectrum of biological and pharmacological activities including anti-cancer activities [1,2]. It has been reported that the introduction of alkyl group or aryl group into the N atom of indolones can significantly increase its cytotoxicity against a variety of cancer cell lines [1][2][3].…”

“…The residue included the prevailing product 5,7-dibromo-1-(2-bromoethyl)indoline-2,3-dione (R f = 0.40, m.p. 375-377 K ; yield 40%) and the title product 5',7'-dibromo-1'-(2-bromoethyl)spiro[ [1,3]dioxolane-2,3'-indolin]-2'-one (R f = 0.5, m.p. 382-383 K; yield 38%).…”

Crystal structure of (Z)-methyl N'-(5,7-dibromo-1-(2-morpholinoethyl)-2- oxoindolin-3-ylidene)hydrazinecarbodithioate, C16H18Br2N4O2S2

“…1H-indole-2,3-dione derivatives possess av ariety of biological activities, including antitumor activity [2].I ntroduction of substituents at the 3-and 5-positions of the indolin-2-one ring have recently led to many derivatives possessing more potent antiumor activities [3,4].Inaddition, the introduction of an alkyl group or aryl group at the Natom of indolin-2-ones enhanced their cytotoxicity againstavarietyofcancercelllines [5,6]. Herein, we report thecrystal structure of oneofthe derivateswhich maybea potential anticancer agent.…”