Isatin, with the chemical name 1H-indole-2,3-dione skeleton, is an important pharmaceutical intermediate that can be used to prepare antitumor drugs, antibacterial drugs, and antimalarial drugs. Isatin also undergoes important chemical reactions such as oxidation, ring expansion, Friedel-Crafts reaction, and aldol condensation. These reactions in turn produce some biologically active compounds such as 2-oxoindole, pancreatin, and indole.

Antitumor drugs

Isatin is a recognized pharmacophore in many clinically approved cancer therapeutics, such as sunitinib and toceranib phosphate. The U.S. Food and Drug Administration (FDA) approved the indole derivative sunitinib (2) (Sutent) for the treatment of advanced renal cancer and gastrointestinal stromal tumors. In addition, toceranib phosphate (3) (Palladia) (Figure 1) is an orally bioavailable analog of sunitinib. It has potent inhibitory activity against members of the split kinase receptor family including vascular endothelial growth factor receptor, epidermal growth factor receptor and Kit. Therefore, toceranib has dual antiangiogenic and direct antitumor activities. Toceranib phosphate (3) has been approved for the treatment of cutaneous mastocytoma.

Antimicrobial agents

In recent years, various isatin derivatives have been screened for their antibacterial activities, and some of them demonstrated promising in vitro and in vivo potency. Antimicrobial agents prepared from isatin include indigo-azoles, indigo-quinolines/quinolones, indigo-furans/coumarins, indigo-hydrazones/(thio)semicarbazones, indigo dimers and indigo-indole hybrids, among others.

Antimalarials

Isatin unit is a special natural product scaffold to which other pharmacological cores can be attached. Therefore, the anti-malarial and anti-malarial activities can be enhanced by linking isatin and quinoline moieties through various linkers. 3-Methylene indolones prepared from isatin are potential antimalarial drugs. Based on this, a series of 3-methylene-substituted indolones were synthesized and their in vitro anti-plasmodial activity against CQR W2 strain was evaluated. Notably, the anti-plasmodial activity can be significantly improved when 4-aminoquinoline is coupled to the 3-methylene part of the indole-2-one skeleton, indicating that these hybrids (IC50: 0.14-0.42 μM) are potential leads for the development of new antimalarial drugs. In addition, the change in carbon chain length between the indoleone and quinoline skeletons has no significant effect on the activity.

In addition, isatin can also be used to prepare isatin-based Schiff, which is usually formed by the condensation of indigo ketone groups with different aromatic primary amines bearing imine or azomethine (–C=N–) functional groups. Isatin Schciff Base has a variety of biological properties, such as anti-tumor, anti-bacterial, anti-inflammatory, anticonvulsant, anti-viral, anti-HIV, antioxidant and central nervous system inhibitory activities.