Molluscicidal hydroxynaphthoquinones and derivatives: correlation between their redox potentials and activity against Biomphalaria glabrata

Journal of the Brazilian Chemical Society

Pinto, Antônio V.¹  Goulart, Marília O. F.¹  Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil¹  Pinto, Maria do Carmo R. F.¹  Correia, Clariane S.¹  Santana, Antônio Euzébio G.¹  Universidade Federal de Alagoas, Maceió, Brazil¹  Ferraz, Patrícia A. L.¹  Lima, Nadja M. F.¹ 

关键词: hydroxyquinones;    molluscicides;    Biomphalaria glabrata;    redox potential;   

DOI  :  10.1590/S0103-50532002000600015

学科分类：化学（综合）

来源: SciELO

【 摘 要 】

Schistosomiasis remains a major public health problem in the developing world with an estimated 200 million people infected and 600 million at risk of infection. It is thus important to apply efficient methods to control the transmission of the disease alongside medical treatment for those already infected. Permanent solutions to limit human contact with polluted water and further contamination of the environment1 require the provision of safe water and appropriate sanitary facilities, but sustained progress in the elimination of schistosomiasis cannot be achieved without back up from other approaches, e.g. snail control.2 The use of molluscicides in the prophylactic treatment promotes the rupture of the evolutionary cycle of Schistosoma mansoni (the causative agent of schistosomiasis) through the destruction of its intermediate host, the snail Biomphalaria glabrata.3 This constitutes the weakest link in the cycle of transmission and is the logic point of attack to control the disease.3 New, safe, and effective molluscicides are urgently needed, but in order to be useful the products must be stable, inexpensive, easily applicable and show high selective toxicity to the target pest.4 Numerous quinones play vital roles in the biochemistry of living cells and exert relevant biological activities. The cytostatic and anti-microbial activities of these quinones emerge by virtue of their ability to act as potent inhibitors of electron transport, as uncouplers of oxidative phosphorylation, as DNA intercalating agents, as bioreductive alkylating agents, and as producers of reactive oxygen radicals by redox cycling under aerobic conditions. In all of these cases the mechanism of action in vivo requires the bioreduction of the quinone as the first activating step.5,6 There are other possible mechanisms of action of the quinones, including sulfhydryl arylation,7 or topoisomerase involvement,8 but these are not based on electron transfer. Among the biologically active quinones, hydroxynaphthoquinones are important anti-cancer9 and anti-protozoal10,11 agents: in particular, lapachol (1) and some of its analogues possess anti-tumour, antibiotic, anti-malarial, anti-inflammatory and anti-ulcer activities.12 Recent results have also demonstrated strong trypanocidal13, 14 and molluscicidal (against B. glabrata) activities14-16 for 1 and its derivatives and analogues. Lapachol is bioactivated by P450 reductase to reactive species which promote DNA scission through the generation of superoxide anion radicals17 by redox cycling. Analysis of the molluscicidal activities of naphthoquinones indicates that simple molecules having an -OH group in the quinoid ring display low activity, whereas those with a -CH3 group in the quinoid ring possess significant activity.4 In the

【 授权许可】

Unknown