Synthesis and Antitumor Activity of 1,5,6-Substituted E-3-(2-Chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones

Abstract

Synthesis and antitumor activity of new E-3-(2-chloro-3-indolylmethylene)-1,3-dihydroindol-2-ones are described. All compounds prepared were active in the primary test (three human cell lines) and entered the second level (60 human cell lines). The most active antitumor derivatives bear the same substituents in the chloroindole ring and are not CDK1 inhibitors. A COMPARE analysis showed that they could act as tubulin binders. In most cell lines, E-3-(2-chloro-5-methoxy-6-methyl-3-indolylmethylene)-1,3-dihydroindol-2-one was a growth inhibitor more potent than vincristine.

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

“…Melting points were determined with an Electrothermal 9100 melting point apparatus (Electrothermal Engineering, Essex, UK) and uncorrected. 1 (3) (2 mmol) and appropriate indole-3-carbaldehyde 4(aee) (2 mmol) in 4 ml of ethanol and 2 ml of water was added 2 g of solid KOH. The reaction mixture was refluxed for at least 12 h. The end of the reaction was monitored by TLC.…”

Cancer fighting cancer: synthesis of the new heterocyclic system diimidazo[1,2-a:1,2-c]pyrimidine

“…2 The last one (number 32 of this series) has been published recently. 3 We called one of our projects, "Cancer…”

“…The first fighter we designed for this project had the structure reported in Figure 1. For the synthesis of this compound, 2,7-disubstituted di-imidazo-[2,1-b:1,2-d]-[1, 3,4]-thiadiazole (compound 5 in Figure 2) was the key intermediate which we endeavored to prepare from 2,5-diamino-1,3,4-thiadiazole 1. 4 Since the reaction with excess of bromoketone did not give the expected results, we analyzed the reaction step by step: one equivalent of 2-bromoacetophenone gave the expected 2-amino-6-phenylimidazo- [ On the other hand, starting from 2,4-diaminopyrimidine we were able to prepare the intermediate for our first target compound, as illustrated in Figure 4.…”

5-Benzoyl-2-(5-bromo-1H-indol-3-yl)-4-(4-methoxyphenyl)-1H-pyrrole-3-carbonitrile

“…Today, analogues based on indole are significant players in a diverse array of markets such as dyes, plastics, agriculture, vitamin supplements, over-thecounter drugs, flavour enhancers and perfumery (Barden, 2011). Indole derivatives exhibit antibacterial, antifungal (Singh et al 2000), antitumor (Andreani et al, 2001), antihepatitis B virus (Chai et al, 2006) and anti-inflammatory (Rodriguez et al, 1985) activities. They are also used as bioactive drugs (Stevenson et al, 2000) and exhibit high aldose reductase inhibitory (Rajeswaran et al, 1999) and antimicrobial activities (Amal Raj et al, 2003).…”