Role of synthetical amynoquinone ethyl 2-(1,4-dioxo-1,4-dihydronaphthalen-2-ylamino) acetate in inhibition of Ehrlich's tumor.

Quinones are naturally or synthetically occurring secondary metabolites that have various bio-dynamics, highlighting their antitumor potential. This has been explored through their selective cytotoxicity, and studies in medicinal chemistry about the relation between biological activity versus chemical structure may lead to the solution of the toxicity problems associated with quinones. In this context, the antitumor effect of a synthetic naphthoquinone, named Ethyl 2-(1,4-Dioxo-1,4-Dihydronaphthalen-2-Ylamino) Acetate, was tested using mice transplanted with Ehrlich ascitic tumor as an experimental model. The acute toxicity test was performed using 30 mice that received the aminoquinone at doses of 100, 200, 300, and 600 mg/kg. After evaluation of the clinical findings in the spontaneous activity tests, the LD50 calculation for the test substance showed low levels of toxicity at doses lower than 244.11 ± 23.29 mg/kg. Thus, three experimental groups were established, where animals transplanted with tumor cells received NaCl vehicle solution (control, n = 6), and the others were treated with 71.7 mg/kg of Methotrexate (n = 6) or 20 mg/kg of Aminoquinone (n = 6). All administrations were intraperitoneal, in a single dose. Three days after the implantation of the tumor cells the animals were weighed daily and evaluated for tumor biometry and development. The treatments occurred five days after the implantation of the tumor cells and were extended for 7 more days. At the end of the 12-day experimental period, all animals were euthanized for biochemical and histopathological analyses of the tumors and vital organs. The spontaneous activity test showed that the amount of responses associated with the nervous system tends to increase with the increase in dosage, highlighting the excitatory effect on the central nervous system in almost all dosages employed, followed by depressant activities on this system. There was a significant tumor reduction, both in animals treated with methotrexate (71.7 %) and in those treated with aminoquinone (91.6 %) in the control group. There was no significant difference in tumor volume between the animals treated with aminoquinone or methotrexate. The histopathological analysis revealed that in both treatments there were fewer mitoses in the tumor mass compared to the control group. However, there was apparent toxicity to the liver, heart, and left kidney in the treatment with methotrexate compared to aminoquinone. The significant capacity for tumor reduction presented by aminoquinone allows pointing it as a promising alternative for the development of a more efficient drug to control tumor development, being necessary for the development of new studies to deepen the knowledge about its mechanisms of action.

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum and in vivo in P. berghei-infected mice.

Malaria is one of the most important tropical diseases and mainly affects populations living in developing countries. Reduced sensitivity of Plasmodium sp. to formerly recommended antimalarial drugs places an increasing burden on malaria control programs as well as on national health systems in endemic countries. The present study aims to evaluate the antimalarial activity of betulinic acid and its derivative compounds, betulonic acid, betulinic acid acetate, betulinic acid methyl ester, and betulinic acid methyl ester acetate. These substances showed antiplasmodial activity against chloroquine-resistant Plasmodium falciparum parasites in vitro, with IC(50) values of 9.89, 10.01, 5.99, 51.58, and 45.79 microM, respectively. Mice infected with Plasmodium berghei and treated with betulinic acid acetate had a dose-dependent reduction of parasitemia. Our results indicate that betulinic acid and its derivative compounds are candidates for the development of new antimalarial drugs.