Abstract
In the present work, we report the synthesis and in vitro anticancer and antimicrobial activity evaluation of a new series of 1-substituted-β-carboline derivatives bearing a 4-benzylidene-4H-oxazol-5-one unity at C-3. The compound 2-[1-(4-methoxyphenyl)-9H-β-carbolin-3-yl]-4-(benzylidene)-4H-oxazol-5-one (11) was the most active derivative, exhibiting a potent cytotoxic activity against glioma (U251), prostate (PC-3) and ovarian (OVCAR-03) cancer cell lines with IC50 values of 0.48, 1.50 and 1.07 µM, respectively. An in silico study of the ADME properties of the novel synthesized β-carboline derivatives was also performed.
Highlights
Natural and synthetic tetrahydro- -carbolines and -carbolines are a class of alkaloids with a large spectrum of important pharmacological properties [1,2,3,4,5,6,7]
With the aim of evaluating the influence of different substituents at position-3 of 1-substituted- carbolines, in this work we propose the incorporation of a benzylidene-4H-oxazol-5-one unity at C-3, expecting an improvement of the antitumor and antimicrobial activities in relation to the most active
The derivatives 5a–c were converted to the respective N-(1-benzylidene-β-carboline-3-carbonyl)-glycine ethyl esters 6a–c by activation of the -carboline-3-carboxylic acids 5a–c with N,N'-dicyclohexylcarbodiimide (DCC) and dimethylaminopyridine (DMAP), in pyridine, followed by treatment with glycine ethyl ester hydrochloride [32]
Summary
Natural and synthetic tetrahydro- -carbolines and -carbolines are a class of alkaloids with a large spectrum of important pharmacological properties [1,2,3,4,5,6,7]. The SAR studies have demonstrated that the introduction of appropriate substituents into the positions −1, −2, −3 and −9 of the -carboline nucleus resulted in more potent antitumor -carboline derivatives, with reduced toxicity. The potential of -carbolines and the importance of the search for new antitumor agents led our group to a continuing study of this class of compounds. We reported the synthesis and in vitro antitumor activities, against a panel of human cancer cell lines, of a series of 1-substituted. The anticancer assay results indicated several compounds with potent anticancer activity, with IC50 values lower than 1.0 M for some of the human cancer cell lines tested [17,18,19]. In addition to the antitumor activity, -carbolines containing the 2-thioxo-1,3,4-oxadiazole group at C-3 exhibited antimicrobial activity towards the fungus
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