Banca de QUALIFICAÇÃO: JOICE CASTELO BRANCO SANTOS

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : JOICE CASTELO BRANCO SANTOS
DATE: 31/03/2020
TIME: 14:00
LOCAL: SALA 1 DO PPGCF
TITLE:

Bisphosphonate-based molecules as potential new antiparasitic drugs

KEY WORDS:

Leishmaniasis; Leishmania amazonensis; Bisphosphonates; Farnesyl diphosphate synthase; Antiparasitic Drugs.

PAGES: 76
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

Leishmaniasis is one of the main neglected tropical diseases caused by several species of parasite of the genus Leishmania responsible for at least twelve million cases of infections worldwide. Despite its importance in terms of public health, treatment of patients is limited and has mainly low levels of efficacy and safety. Bisphosphonates are compounds that inhibit the enzyme farnesyl diphosphate synthase (FPPS) that acts in the early stages of ergosterol synthesis that maintains the integrity of the lipid bilayer of the disease-causing parasite. In this sense, the main objective of this project is to evaluate the antiparasitic activity of synthetic compounds based on bisphosphonates in axenic cultivation of Leishmania amazonensis. Twenty four bisphosphonate-based compounds covering a concentration range of 100μM to 1μM were evaluated against L. amazonensis promastigotes for a period of 24 hours using the resazurin colorimetric assay. IC50 values of compounds that inhibited parasitic activity in a range greater than 50% at the initial screening concentration were examined, and these same compounds were subjected to the cell death profile assay and molecular docking against the FPPS enzyme. Parasitic activity showed a significant reduction in the highest concentration in compounds 1656 and 1662, with inhibition values of 100 and 88%, respectively. Moderate activity for 1651 (40%) and 1652 (42%). The other compounds showed inhibition below 40%. The IC50 values for 1656 and 1662 were 58.39 and 52.86 μM, respectively. And in the cell death profile assay only compound 1662 showed apoptosis at concentrations of 100 μM (3.84%) and 50 μM (1.75%) and necrosis of 17.7% and 12.4% for concentrations of 100 μM and 50 μM, respectively. Compound 1656 showed only necrosis with values of 2.70 and 2.73%, in the same order of concentration. In molecular docking, both compounds acted on the FPPS enzyme through the interaction between hydrogen bonds. These results show that synthetic compounds based on bisphosphonates have been shown to be potential candidates for leishmaniasis chemotherapy. Since the main measures to control this disease are through therapeutic treatment programs, this project encourages further studies to identify active compound (s) for the control of leishmaniasis.

BANKING MEMBERS:
Externa à Instituição - CLÁUDIA JASSICA GONÇALVES MORENO - UFRN
Presidente - 1893445 - EUZEBIO GUIMARAES BARBOSA
Externa à Instituição - WENDY MARINA TOSCANO QUEIROZ DE MEDEIROS - IFBA