Banca de QUALIFICAÇÃO: MATHEUS LOPES SILVA

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : MATHEUS LOPES SILVA
DATA : 29/07/2022
HORA: 14:00
LOCAL: apresentação via google meet (link - https://meet.google.com/vwd-roja-fyn)
TÍTULO:

EVALUATION OF ANTI-Trypanosoma cruzi ACTIVITY OF CONSTITUENTS CHEMICALS ISOLATED FROM Baccharis sphenophylla Dusén ex Malme (ASTERACEAE)

PÁGINAS: 68
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
ESPECIALIDADE: Química dos Produtos Naturais
RESUMO:

Chagas disease, whose etiologic agent is the protozoan Trypanosoma cruzi, is considered the
most neglected of the neglected tropical diseases, given the scarce therapeutic arsenal, absence of
economic interest and public policies aimed at its eradication. Phytochemical studies involving
extracts from plants of the genus Baccharis led to the isolation of active compounds against the different
morphogenetic forms of T. cruzi. Thus, the hexane extract of aerial parts of Baccharis
sphenophylla Dusén ex Malme (Asteraceae) was selected for biomonitored phytochemical investigation. O
showed activity against the amastigote forms of T. cruzi and was submitted to successive stages
chromatographic. From this study, the not yet reported compound 7α-hydroxy-ent-abieta8(14),13(15)-dien-16,12β-olide (1), three known diterpenes – ent-caur-16-en- 19-oic, (2), acid
grandifloric (3) and 15β-tiglinoyloxy-ent-kaur-16-en-19-oic acid (4), two sesquiterpenes – spathulenol (5)
and oplopanone (6) – as well as the phenylpropanoid hexacosyl p-coumarate (7). The isolated compounds
were characterized by NMR and AR-MS spectra and were evaluated in vitro for activity against
amastigote and trypomastigote forms of the parasite. In addition, the activity of compounds 1 – 7 against
NCTC cells were also evaluated. Compounds 1 and 7 showed efficacy against amastigote forms of the
parasite with 50% effective concentration (EC50) in the values of 21.3 and 16.9 μM, respectively. Both
the compounds also exhibited reduced toxicity against NCTC cells, showing values of
50% cytotoxic concentration (CC50) greater than 200 μM, thus configuring index values of
selectivity (IS) higher than 9.4 and 11.9, respectively. Compounds 2 and 4 showed efficacy against
trypomastigote forms of the parasite with EC50 values of 10.6 and 2.4 μM, respectively. While the
compound 2 was nontoxic against NCTC cells (CC50 > 200 μM), compound 4 showed toxicity
moderate with a CC50 value corresponding to 83.5 μM. Which thus set IS values
corresponding to > 18.8 and 34.8 for compounds 2 and 4, respectively. Given the activity observed for
compounds 2 and 4 against trypomastigote forms, they were investigated as to the mechanism
of killing action of the parasite. This study revealed that compounds 2 and 4 act by destabilizing
of acidocalcissomes, organelles responsible for osmotic regulation of the parasite. The obtained results
were peer-reviewed and published in the articles: Chemical Constituents from Aerial Parts of Baccharis
sphenophylla and Effects against Intracellular Forms of Trypanosoma cruzi (https://doi.org/10.1002/cbdv.202100466) and Ent-kaurane diterpenes isolated from n-hexane extract of
Baccharis sphenophylla by bioactivity-guided fractionation target the acidocalcisomes in Trypanosoma
cruzi (https://doi.org/10.1016/j.phymed.2021.153748), being the first chosen to configure the cover of the
issue 10, volume 18 of the journal Chemistry & Biodiversity (https://doi.org/10.1002/cbdv.202100695).
Therefore, this work suggests that compounds 1, 2, 4 and 7 can be used as prototypes for the
development of new and selective semisynthetic derivatives against intracellular and
cruzi, opening new avenues for the development of new drugs and therapies
alternatives for Chagas disease.

MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1623577 - JOAO HENRIQUE GHILARDI LAGO
Membro Titular - Examinador(a) Externo à Instituição - JOSUE DE MORAES - UNG
Membro Titular - Examinador(a) Externo à Instituição - EDGARD ANTONIO FERREIRA - UPM
Membro Suplente - Examinador(a) Externo à Instituição - THAIS ALVES DA COSTA SILVA - SENAI