Banca de DEFESA: JOICE CASTELO BRANCO SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : JOICE CASTELO BRANCO SANTOS
DATE: 30/10/2020
TIME: 09:00
LOCAL: Videoconferência
TITLE:

Screening and evaluation of the anti-Leishmania amazonensis activity of bisphosphonate-based synthetic compounds

KEY WORDS:

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

PAGES: 84
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 initial 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 Leishmania amazonensis. Twenty four compounds covering a concentration range of 100µM to 1µM were evaluated against L. amazonensis promastigotes for a period of 24 hours through the colorimetric assay of resazurin, and those that obtained inhibition greater than 50% of the initial concentration were selected to determine values IC50. In addition, molecular docking was evaluated against the L. major FPPS enzyme and the possible mechanisms of the antiparasitic activity of these compounds. Parasitic screening showed a significant reduction in the highest concentration in compounds 1656 and 1662, with inhibition values of 100% (IC50 = 58.39 µM) and 88% (IC50 = 52.86 µM), respectively. In molecular docking, compounds 1656 and 1662 interacted with the FPPS enzyme by bonding with hydrogen bonds. And in the double fixation assay by Annexin V-FITC and IP, compound 1662 showed apoptosis at concentrations of 100 µM (3.84%) and 50 µM (1.75%) and necrosis at 100 µM (17.7%) and 50 µM (12.4%). Only compound 1656 showed necrosis with values of 2.70 and 2.73%, in the same concentration sequence. 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:
Interno - 1639820 - ARNOBIO ANTONIO DA SILVA JUNIOR
Presidente - 2275890 - MARCELO DE SOUSA DA SILVA
Externa à Instituição - WENDY MARINA TOSCANO QUEIROZ DE MEDEIROS - IFBA