Targeting tubulin polymerization by novel 7-aryl-pyrroloquinolinones: Synthesis, biological activity and SARs was written by Bortolozzi, Roberta;Mattiuzzo, Elena;Dal Pra, Matteo;Sturlese, Mattia;Moro, Stefano;Hamel, Ernest;Carta, Davide;Viola, Giampietro;Ferlin, Maria Grazia. And the article was included in European Journal of Medicinal Chemistry in 2018.Name: 6-Nitro-1H-indole This article mentions the following:
For wide-ranging SARs, a series of 7-arylpyrroloquinolinones, e.g., I (R1 = Me, Ph, 1-naphthyl, 1,3-benzodioxol-5-yl, etc.; R2 = Et, n-C18H37), was synthesized through a robust procedure. For comparison with the reference 3-ethyl-7-phenyl-3H-pyrrolo[3-2-f]quinolin-9-one, the angular geometry and substituents at the 3 and 7 positions were varied to explore interactions inside the colchicine site of tubulin. Among the new compounds synthesized, potent cytotoxicity (low and sub-nanomolar GI50 values) was observed with compounds I (R1 = 1-naphthyl, 1,3-benzodioxol-5-yl; R2 = Et), both more potent than 3-ethyl-7-phenyl-3H-pyrrolo[3-2-f]quinolin-9-one, in both leukemic and solid tumor cell lines. Neither of the two above compounds I induced significant cell death in normal human lymphocytes, suggesting that these compounds may be selectively active against cancer cells. In particular, I (R1 = 1,3-benzodioxol-5-yl; R2 = Et) (II) was a potent inducer of apoptosis in the A549 and HeLa cell lines. With both compounds, induction of apoptosis was associated with dissipation of the mitochondrial transmembrane potential and production of reactive oxygen species, indicating that cells treated with these compounds followed the intrinsic pathway of apoptosis. Moreover, immunoblot anal. revealed that the compound II even at 50 nM reduced the expression of anti-apoptotic proteins such as Bcl-2 and Mcl-1. Finally, mol. docking studies of the newly synthesized compounds demonstrate that active pyrroloquinolinone derivatives strongly bind in the colchicine site of β-tubulin. In the experiment, the researchers used many compounds, for example, 6-Nitro-1H-indole (cas: 4769-96-4Name: 6-Nitro-1H-indole).
6-Nitro-1H-indole (cas: 4769-96-4) belongs to indole derivatives. Indole, also called Benzopyrrole, a heterocyclic organic compound occurring in some flower oils, such as jasmine and orange blossom, in coal tar, and in fecal matter.Indole was synthesized in moderate yield via an o-naphthoquinone catalyzed tandem cross-coupling of substituted aniline and benzylamine under aerobic oxidation conditions.Name: 6-Nitro-1H-indole
Referemce:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles