Molluskicidal activity of 3-aryl-2-hydroxy-1,4-naphthoquinones against Biomphalaria glabrata.

Schistosomiasis is the second most prevalent parasitic infectious disease after malaria, which affects millions of people worldwide and causes health and socioeconomic problems. The snail Biomphalaria glabrata is an intermediate host for the helminth, which is the causative agent of schistosomiasis: Schistosoma mansoni. One crucial strategy for controlling the disease is the eradication of the snail host. Niclosamide is the unique molluskicide applied in large-scale control programs, but its selectivity to other species is not adequate. Therefore, there is an urgent need to develop new molluskicides that are inexpensive, safe, and selective. Quinones are ubiquitous, playing important biological roles in fungi, plants, and others. Many synthetic molecules with relevant biological activities that contain the quinone nucleus in their structure are on the market in the therapy of cancer, malaria, or toxoplasmosis, for example. Derivatives of quinones are tools in the development of new molluskicides for Abbott laboratories. In the present work, 3-aryl-2­hydroxy-1,4-naphthoquinones (ANs) were tested for molluskicide activity against Biomphalaria glabrata. The lethal concentration was determined for 48 h of continuous exposure. The naphthoquinones were found to have molluskicide properties. AN-15 was recorded as the highest mortality. Additionally, this analog exhibited in silico reduced ambient toxicity when compared to niclosamide. The findings of this study demonstrate that 3-aryl-2­hydroxy-1,4-naphthoquinones are effective for the management of Biomphalaria glabrata under laboratory conditions.

Novel properties of melanins include promotion of DNA strand breaks, impairment of repair, and reduced ability to damage DNA after quenching of singlet oxygen.

Melanins have been associated with the development of melanoma and its resistance to photodynamic therapy (PDT). Singlet molecular oxygen ((1)O(2)), which is produced by ultraviolet A solar radiation and the PDT system, is also involved. Here, we investigated the effects that these factors have on DNA damage and repair. Our results show that both types of melanin (eumelanin and pheomelanin) lead to DNA breakage in the absence of light irradiation and that eumelanin is more harmful than pheomelanin. Interestingly, melanins were found to bind to the minor grooves of DNA, guaranteeing close proximity to DNA and potentially causing the observed high levels of strand breaks. We also show that the interaction of melanins with DNA can impair the access of repair enzymes to lesions, contributing to the perpetuation of DNA damage. Moreover, we found that after melanins interact with (1)O(2), they exhibit a lower ability to induce DNA breakage; we propose that these effects are due to modifications of their structure. Together, our data highlight the different modes of action of the two types of melanin. Our results may have profound implications for cellular redox homeostasis, under conditions of induced melanin synthesis and irradiation with solar light. These results may also be applied to the development of protocols to sensitize melanoma cells to PDT.