Antitumor Activity of Bis-indole Derivatives

Abstract

This paper reports the synthesis of compounds formed by two indole systems separated by a heterocycle (pyridine or piperazine). As a primary screening, the new compounds were submitted to the National Cancer Institute for evaluation of antitumor activity in the human cell line screen. The pyridine derivatives were far more active than the piperazine derivatives. For the study of the mechanism of action, the most active compounds were subjected to COMPARE analysis and to further biological tests including proteasome inhibition and inhibition of plasma membrane electron transport. The compound bearing the 5-methoxy-2-indolinone moiety was subjected to the first in vivo experiment (hollow fiber assay) and was active. It was therefore selected for the second in vivo experiment (human tumor xenograft in mice).In conclusion we demonstrated that this approach was successful since some of the compounds described are much more active than the numerous, so far prepared and tested 3-indolylmethylene-2-indolinones.

Synthesis, anticancer activities and molecular modeling studies of novel indole retinoid derivatives

“…All spectral data were in accordance with assumed structures. The trans conformation of these derivatives were confirmed by a reference 3 J HH value of 16 Hz obtained for the HC]CH group of (E)-3-(6-fluoro-1H-indol-3-yl)acrylic acid [33].…”

Bisindole-PBD regulates breast cancer cell proliferation via SIRT-p53 axis

“…46 In this present study, it has been shown that bisindole conjugate 5b exhibited profound control over growth factor signaling pathway mediated by PI3K/ AKT/mTOR and modulate the balance between survival signals as well as apoptotic signals via SIRT and p53 axis in breast cancer cell-lines. Till date not many SIRT inhibitors have been studied in metabolic disorders, nor their regulation of balance between growth factor signaling and p53 mediated apoptotic pathway in breast cancer cells is understood.…”

Pathways of Electrochemical Oxidation of Indolic Compounds

“…Pharmacological studies of indolic compounds reported a wide variety of important biological properties such as anti-inflammatory [2,3], analgesic [3], antibacterial [4], antifungal [5], neuroprotective [6,7], antitumour [8][9][10] and antioxidant properties [11].…”