Banca de DEFESA: MARINA BRANDÃO DA FONSECA

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : MARINA BRANDÃO DA FONSECA
DATA : 28/01/2020
HORA: 09:00
LOCAL: Pavilhão de Química, sala 49
TÍTULO:

Optimization of the prototype LDQMC-014: an acridinone inhibitor
of Tubulin polymerization.

PALAVRAS-CHAVES:

Multicomponent reaction; cancer; Tubulin.

PÁGINAS: 129
GRANDE ÁREA: Ciências Exatas e da Terra
ÁREA: Química
SUBÁREA: Química Orgânica
RESUMO:

lethal, and its triple negative subtype has the highest mortality rate. There is no specific treatment
for the triple negative subtype, and the high rates of disease recurrence and metastasis make it
necessary to search for new forms of treatment. A multicomponent reaction is a type of reaction
for chemical synthesis, where three or more reagents react to form a single product with a high
degree of chemical diversity, and the Hantzsch reaction is one of the first reactions of this type
reported. In the present work, a series of molecules were synthesized, based on the Hantzsch
reaction, and similar in structure to natural products such as Colchicine and Podophyllotoxin
(which have proven antiproliferative activities), which aim to be an optimization of the prototype
LDQMC-014 (7-(3,4,5-trimethoxyphenyl)-9,10,11,12-tetrahydrobenzo[c]acridin-8(7H)-one),
the results of which in previous work demonstrate good cytotoxic activity in vitro, having a
satisfactory tubulin polymerization inhibition profile (widely validated target as anticancer).
Varied yields were obtained with confirmation oh the structure by carbon and hydrogen NMR.
Since LDQMC-014 obtained satisfactory results, it was sought to optimize the synthesis results.
Systematic changes were made in the synthesis parameters, which promoted an increase of more
than 78 % in the reaction yield. The enantiomers of LDQMC-014 were separated by chiral
chromatography, which provided good enantiomeric separation, which subsequently allowed
the determination of the absolute configuration of the asymmetric center present by circular
dichroism. Once the enantiomers were isolated, their biological evaluations were performed in
order to determine their activity, as well as a molecular modeling study to predict the interaction
of the isolated enantiomers with the Tubulin protein. That enantiomers interact differently with
the protein in both the in silico and the in vitro tests. The molecular modeling study was extended
to all intended acridinones to predict a possible interaction with the Tubulin protein. A cell
migration test (Wound Healing) was performed for some of the obtained acridinones, which
determined the inhibition profile of cell migration, a desired characteristic in metastasis cases.

MEMBROS DA BANCA:
Presidente - 1735975 - CEDRIC STEPHAN GRAEBIN
Interno - 1700480 - ARTHUR EUGEN KUMMERLE
Interna - 1979542 - RENATA BARBOSA LACERDA
Externo à Instituição - JONES LIMBERGER - PUC - RJ
Externo à Instituição - VITOR SUETH SANTIAGO - IFRJ