Synthesis and cytotoxicity of novel 3-amino-4-indolylmaleimide derivatives

Abstract

In an attempt to develop potent and selective antitumor agents, a series of novel 3-amino-4-indolylmaleimides were designed and synthesized. The reaction showed high regioselectivity. The structure of compound 7a was determined by an X-ray single crystal diffraction method. The cytotoxicities of the title compounds were evaluated against HeLa, SMMC 7721 and HL 60 cancer cell lines by a standard MTT assay in vitro. The pharmacological results showed that some of the title compounds displayed moderate or high cytotoxic activity against the tested cell lines. Compound 7d was the most promising compound against the tested cancer cell lines. Structure-activity relationships are discussed based on the experimental data obtained. A hydroxyethylamino group at the 3-position in the side chain of indolylmaleimide is associated with an increase in cytotoxicity.

Efficient Pd‐catalysed Synthesis of 3‐Amino‐4‐indolylmaleimides and 3‐Amido‐4‐indolylmaleimides

“…Further, acylation of 7 resulted 3-amido-4-indolylmaleimides (8) (Scheme 1c). [10] As a continuation of our ongoing research program in synthesis of indole based biologically active compounds, [11][12][13][14] we were interested in the synthesis of 3-amino-4-indolylmaleimide and 3-amido-4-indolylmaleimide from a common precursor for their rapid access. Recently, we have developed Buchwald-Hartwig methodologies to install amine and amide auxochromes in various fluorescent molecules.…”

“…treated 3‐bromo‐4‐indolylmaleimide (6) with sodium azide to get 3‐azideindolylmaleimide, which was reduced by PPh 3 to give 3‐aminoindolylmaleimides (7) . Further, acylation of 7 resulted 3‐amido‐4‐indolylmaleimides (8) (Scheme 1c) [10] …”

Design and synthesis of indole-benzimidazole hybrid molecules and evaluation of their in-vitro cytotoxic activities

“…Benzimidazoles are a class of aromatic, bicyclic, heterocyclic chemical compounds that share the basic structure of 6-membered benzene united to 5-membered imidazole. These are the important class of heterocyclic scaffolds which have diverse biological activities and clinical applications, compounds carrying benzimidazole nucleus have been reported to have antiviral [32][33][34], anticancer [35], antibacterial [36], antimalaria [37], antifungal [38], antihelminthic [39], antiprotozoal (Entamoeba histolytica and Trichomonas vaginalis) and anticancer activities [40].…”

BF3-OEt2 Catalyzed C3-Alkylation of Indole: Synthesis of Indolylsuccinimidesand Their Cytotoxicity Studies

“…The properties like anticancer [ 1 , 2 ], antioxidant [ 3 , 4 , 5 ], antirheumatoidal [ 6 , 7 ] and anti-HIV [ 8 , 9 , 10 ] has made indole a privileged scaffold and its derivatives such as indolylsuccinimide are important intermediates in organic synthesis and pharmaceuticals [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. The indole ring system is present in many commercially marketed drugs ( Figure 1 ) [ 19 , 20 , 21 ].…”