Synthesis and Antimalarial Activity of E‐2‐Quinolinylbenzocycloalcanones.

Abstract

Compounds (III) are identified as novel promising antimalarial agents. -(CHARRIS*, J. E.; DOMINGUEZ, J. N.; GAMBOA, N.; RODRIGUES, J. R.; ANGEL, J. E.; Eur. J. Med. Chem. 40 (2005) 9, 875-881; Lab. Sint. Org., Fac. Farm., Univ. Cent. Venezuela, Caracas 1051, Venez.; Eng.) -R. Staver 07-154

Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine

“…Particular attention has been paid to the compound IQ, which was shown to be able to reduce and delay the progression of malaria, decreasing the parasitaemia level by 24% compared to non-treated mice (control) and increasing survival rate up to 12 days over controls. This compound inhibited haemoglobin proteolysis and ß-haematin formation in vitro, suggesting a possible mechanism similar to that of CQ for its antimalarial activity (Charris et al 2005).…”

“…On the other hand, both quinolines have reported to inhibit haeme crystallisation (Chong & Sullivan 2003, Charris et al 2005). This porphyrin is toxic to cells by way of free radical-dependent mechanisms (Kumar & Bandyopadhyay 2005).…”

“…Synthesis of IQ -The compound was synthesised by a base-catalysed Claisen-Schmidt condensation according to Charris et al (2005). In short, a mixture of the 2-chloro-3-formylquinoline (1 mmol), 4-methoxy-1-indanone (1 mmol) and sodium methoxide (catalytic) in methanol (8 mL) was stirred at RT overnight.…”

“…E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) proved to be the best compound tested. This compound was able to decrease parasitaemia levels and increase post-infection survival in Plasmodium berghei-infected mice (Charris et al 2005). On the other hand, some quinoline compounds currently in use exert their activities by increasing oxidative stress in the parasitised erythrocyte.…”

Synthesis of 7-chloroquinolinyl-4-

“…Indeed, a previous study has shown that quinolines and chalcones exihibited potent antimalarial activities, inhibiting heme crystallization, globin proteolysis and showing also in vivo effects in a malaria murine model [20], representing new alternatives which needs to be taken on consideration in further studies. In this work we tested compounds 5-19 for their effects as inhibitors of β-hematin formation and inhibitors of hemoglobin proteolysis in vitro.…”