Design, synthesis and in vitro and in vivo antitumor activities of novel β-carboline derivatives

Synthesis and Biological Evaluation of Novel .BETA.-Carbolines as Potent Cytotoxic and DNA Intercalating Agents

“…1-Methyl-b-carboline-3-carboxaldehydes 1-6 were prepared from the L-tryptophan via six steps including the Pictet-Spengler condensation, esterification, aromatization, N-alkylation or N-arylation, reduction and oxidation as previously described. [26][27][28] The reaction of compounds 1-6 with the corresponding diamines to form schiff bases took place readily at room temperature in good yield. The crude schiff bases without further purification were directly reduced with NaBH 3 CN in anhydrous methanol to give the target b-carbolines 1a, 2a-d, 3a-d, 4a-d, 5a-d and 6a-d (Table 1) in 40-78% yield.…”

“…[2][3][4][5][6][7][8][9] Recent reports [10][11][12][13][14][15][16][17] have pointed out b-carbolines as a class of potential antitumor agents, which was discovered to function their antitumor activity through multiple mechanisms, such as intercalating into DNA, 11,18) inhibiting topoisomerase I and II, 13) CDK, [19][20][21] MAPKAP-K2, 22) MK-2, 23) PLK1 24) and kinesin Eg5. 25) Recently, our group investigations [26][27][28][29][30][31] on the synthesis of a variety of b-carboline derivatives and the evaluation of their antitumor activities unraveled that b-carbolines had potent antitumor activities and the activities were correlated to both the planarity of the molecule and the presence of the ring substituents. Structure-activity relationships (SARs) analysis suggested that the introduction of appropriate substituents into position-2, 3 and 9 played a vital role in determining their antitumor effects, and the n-butyl, benzyl or phenylpropyl substituents at position-9 was suitable pharmacophoric group giving rise to some potent antitumor agents.…”

Synthesis and structure of novel ferrocene-containing β-carbolines including polycondensed derivatives with the elements of planar-, central- and conformational chirality

“…In the recent decades it was also demonstrated that -carboline alkaloids may have a pronounced potential as anti-cancer agents [7][8][9][10][11][12][13][14][15][16], which can act through different mechanisms including eg. DNA-intercalation [17], inhibition of Topoisomerase I and II [18] and CDK (cyclindependent kinases) [19,20].…”

Synthesis,in vitroAntiproliferative and Anti-Mycobacterium tuberculosisActivities of Novel β-Carboline Derivatives

“…[7][8][9][10][11][12][13][14] Our research group demonstrated that β-carboline derivatives with various substituents at positions-1, 3 and 9 of the β-carboline skeleton presented significant in vitro antitumoral, antiviral, antitrypanosomal and antileishmanial activities. [15][16][17][18][19][20][21][22][23] Other studies have shown that β-carboline derivatives with a methyl-substituted group at position-1 and a guanidinium group-terminated side chain at C-3 exhibited anti-HIV-1 activity in MT4 cells by hindering the essential interaction of the regulatory protein Tat with trans-activation response region (TAR).…”