Synthesis of dihydroisoindolo[2, 1-a]quinolin-11-ones, their in silico ADMET properties and in vitro antitumor activities. Issue 69 (19th November 2020)

• Record Type: Journal Article
• Authors: Merchán-Arenas, Diego R.; Sojo, Felipe; Arvelo, Francisco; Kouznetsov, Vladimir V.
• Is Part Of: RSC advances. Volume 10:Issue 69(2020)
• Page Start: 42287
• Page End: 42296
• Publication Date: 2020-11-19
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d0ra04555a
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : We synthesized a series of dihydroisoindolo[2, 1- a ]quinolin-11-ones using the imino Diels–Alder reaction and evaluated their biological properties, finding a new hit in anticancer research. Abstract : We evaluated the antitumoral activity of diverse series of 5-aryl-dihydroisoindolo[2, 1- a ]quinolin-11-ones, AIIQ (Aryl IsoIndolo-Quinoline, 4a–m ), and 5-vinyl dihydroisoindolo[2, 1- a ]quinolin-11-ones, VIIQ (Vinyl IsoIndolo-Quinoline, 6a–l ), obtained using three component imino Diels–Alder (DA) reaction of anilines, o -phthalaldehyde and dienophiles. The first series was obtained in previous work employing isoeugenol and anethole as dienophiles, whereas the vinyl series was synthesized in high yields (75–90%) using isoprene as a dienophile. The cytotoxic activity of both AIIQ and VIIQ series was evaluated against four cancer lines, identifying a new lead compound 4h from the AIIQ series, active against MCF-7 (310 nM), SKBR3 (1434 nM), PC3 (210 nM) and HeLa (79 nM) cells with high selectivity. In addition, in silico ADMET properties for the two series were assessed and discussed.