Planejamento, síntese e avaliação farmacológica de novos candidatos a protótipos de fármacos antitumoral análogos ao composto LQFM 030
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Data
2015-03-10
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Universidade Federal de Goiás
Resumo
Neoplasmas have been a major cause of death worldwide, with that the search for new candidates
for prototypes of more effective anti-tumor drugs, safe and with fewer side effects when compared
to those already available already in therapy, it is essential and fundamental importance. With this
research goal, we developed the design, synthesis and pharmacological evaluation in order to obtain
new candidate of heterocyclic antitumor drugs prototypes (46a-46Q, 48a-48s, 51a-51m, 50m-50a,
53b, 54b, 56b and 58b) and vectorized micronutrient (60) and nanostructures (63) drawn from
LQFM 030 (37) prototypes, in that it (37) was obtained by simplifying molecular strategy nutlin
from compound (34) . The route chosen to obtain the heterocyclic compounds (46Q-46a, 48a-48s,
51a-51m, 50m, 50a, 53b, 54b, 56b and 58b) resulted in yields ranging from 32-77%, where all
synthesized compounds were elucidated through the use of Nuclear Magnetic Resonance
dimensional and two-dimensional (NMR) and Infrared (IR). Two methodologies have been
developed (A and B) for the synthesis of intermediate pyrazole compounds and formylated acid,
wherein the first method was conventional and the second was by heating with microwaves, which
have obtained gain in time and / or increasing the yield of these synthetic steps when comparing
with the conventional method (A). The synthesized compounds were tested for cytotoxicity assays
by MTT method on the cell line K562 leukemic ie, and B16F10 melanoma ie, where the cytotoxic
profile was evaluated using the IC50 = 70 uM for K562 cells and IC 50 = 64, 7 uM to line B16F10,
both using an exposure time of 48 hours. K562 cells for six compounds LQFM ie 88, 108, 165,
166, 168 and 169 showed higher cytotoxic profile when compared to the prototype LQFM030
compound (37). Regarding the B16F10 line, six other compounds LQFM ie 126, 127, 165, 166 and
169 showed a better cytotoxic profile when compared to the prototype compound LQFM030.
Given the results, we can conclude that the planning strategy employed to obtain the study
compounds was validated, and against the cytotoxic research profile of 46a-46Q, 48a-48s, 51a-
51m, 50m-50a, 53b, 54b , 56b and 58b, and have a perspective vectorization and nanostructuring
of the best compounds evaluated for each type of cell line K562 and B16F10 ie, aiming at
optimizing the antitumor activity
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Palavras-chave
LQFM030 , Nutlin , Pirazola , Nanoestruturação , K652 , Nutlin , Pyrazole , Nanostructuring , B16F10
Citação
CARVALHO, Flávio Silva de. Planejamento, síntese e avaliação farmacológica de novos candidatos a protótipos de fármacos antitumoral análogos ao composto LQFM 030. 2015. 498 f. Tese (Doutorado em Química) - Universidade Federal de Goiás, Goiânia, 2015.