2-Arylindoles: A Privileged Molecular Scaffold with Potent, Broad-Ranging Pharmacological Activity

Abstract

Privileged structures bind to multiple receptors with high affinity, thus aiding the development of novel biologically active compounds. Indoles are classed as privileged structures, and as a result of the indole nucleus being present in a broad range of biologically active molecules, it has been suggested that indoles probably represent the most important of all structural classes in drug discovery. Amongst the indole class of compounds is a particular subset - 2-arylindoles - which appear to be a most promising lead for drug development. This review summarises the wide-ranging activities of 2-arylindoles and some of their important biological activities reported in the literature over the past two decades.

Heterocyclic scaffolds as promising anticancer agents against tumours of the central nervous system: Exploring the scope of indole and carbazole derivatives

“…[87] Indole ethyl isothiocyanates were investigated due to their similarity to benzyl isothiocyantes and phenyl ethyl isothiocyanes, both of which have been reported to have anti-cancer activity in a range of cancers. [6,[88][89][90] Of all the indole ethyl isothiocyanates tested, 7-methyl indole-3-ethyl isothiocyanate (7Me-IEITC, Figure 19) was found to be the most active, and when tested on a range of neuroblastoma cell lines was found to have an IC50 in the range of 2.5-5 µM, while not affecting the primary control cells. 7Me-IEITC activates the apoptoptic markers caspase-3, caspase-8 and caspase-9, activates the pro-apoptoptic p38 mitogen-activated protein kinases and signaling pathway SAPK/JNK, and downregulates AKT.…”

“…Because of the rapid chemoresistance developed by many brain cancers, these drugs alone simply aren't sufficient for long-term treatment. The indole moiety has been described as a privilaged structure [6] as it is a structure that appears extensively in many unrelated areas of biology and medicine, and depending on substituents can have a diverse range of effects. The indole nucleus can be found in compouds as diverse as the hormone serotonin, the amino acid tryptophan, the psychedelic drug LSD and the antimigrane drug rizatriptan (Figure 1).…”

“…It is believed by many to be the most ubiquitous and important privilaged structure known. [6,7] This review focuses on the development of drugs for the treatment of tumours of the central nervous system which are structurally based on the indole, carbazole and indolocarbazole scaffolds ( Figure 2). In doing so, the literature was searched using Thomson Reuters' Web of Knowledge™ for articles containing both a classification of tumours of the central nervous system and either the term "*indol*" or "*carbazol*", and no restraint on publication date was used.…”

Unconventional Knoevenagel-type indoles: Synthesis and cell-based studies for the identification of pro-apoptotic agents

“…Indole is a privileged scaffold for drug discovery [1,2]. Indole derivatives have been described as useful chemical templates in different therapeutic areas, including the treatment of neurodegenerative diseases [3][4][5], psychiatric disorders [6] and inflammation [7,8].…”

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

“…1, II ) [3]. Moreover, the indole moiety is considered as a privileged structure since it is encountered in many bioactive molecules and arylindoles [4] are particularly active when substituted in 2-position [5]. 1,2-Diarylindoles have been reported to display interesting pharmacological activities, e.g., as estrogen receptor ligands (Fig.…”