Logical synthetic strategies and structure-activity relationship of indolin-2-one hybrids as small molecule anticancer agents: An overview

This review focuses on the potential of indolin-2-one in the treatment of cancer as a chemotherapeutic nucleus and highlights significant recent progress in the synthetic development of indolin-2-one as an antitumor agent. The indolin-2-one framework is often considered to be a privileged heterocycle present in medicinally useful natural and synthetic compounds. Logical strategies in small molecule drug discov-ery, such as molecular hybridization, bioisosteric substitution, scaffold hopping designs, pharmacophore linking / hybridization, modern synthetic methods, and so on, have been extensively discussed in this article to find the best cancer chemotherapeutic agents carrying the indolin-2-one scaffold. Various acid or base catalyzed reactions are studied to investigate the reactivity of indolin-2-ones at the beta-carbon and -NH positions. Chemical modifications of the FDA approved indolin-2-ones at -C(3),-N and the aryl portion of the scaffold for the treatment of various indications of cancer are presented. Molecular dissection of existing anticancer drugs to obtain better new lead molecule is discussed. The structure-activity relationship of indolin-2-ones chemotype has been thoroughly researched over the last few decades by in vitro cytotoxic assessment of different human cancer cell lines and tyrosine kinase receptors. Mechanism of cytotoxic action of some indolin-2-one molecular hybrids in conjunction with various heteroaryl based moieties is discussed herein. Synthetic approaches, novel methods involving different catalysts and chemical reagents, cell and receptor selectivity of small molecules described in this article would be of interest to future synthetic and medicinal chemists in order to pursue their research into indolin-2-one and cancer as a disease target. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

This review discusses the potential of indolin-2-one in cancer treatment, recent progress in synthetic development, logical strategies in small molecule drug discovery, and the structure-activity relationship of indolin-2-one chemotype.