ABSTRACT
INTRODUCTION: Cancer, despite advances in diagnostic and treatment issues, is the second leading cause of death in the world, accounting for 9.6 million deaths in 2018, or one in every six registered deaths [1]. Semicarbazones and thiosemicarbazones are important classes of compounds in medicinal chemistry, as they have different pharmacological activities. These activities are linked to some structural specificities [2, 3], such as Schiff base functional group, that plays a relevant role in the coordination chemistry of this class compounds [4]. AIMS: Evaluate the cytotoxic activity of semicarbazone and thiosemicarbazone derivatives in tumor cell lines and normal human cells, showing percentage of inhibition (%CI) and IC50. METHODS: The products (LSS2, LSS4, LSS6 and LS12) were synthesized, characterized and obtained by LABSINFA - UFPE, under the coordination of Prof. Dr. Dalci José Brondani. For the cytotoxicity assay, HT-29, HeLa, K562, Jukart and P815 tumor cells were used. Cells were seeded in 96-well plates, in the presence of compounds diluted in DMSO at a single concentration of 25 µg/mL. The MTT assay was performed in 72 h and the absorbance was measured in a microplate reader at a wavelength of 560 nm. Inhibitory concentration (CI%) and IC50 were calculated by non-linear regression using GraphPad Prism 8.0.1. RESULTS AND DISCUSSION: The compounds tested obtained a %CI that ranged from 54,1± 2.7 to 100 % and IC50 that ranged from 3.9 ± 0.1 to 75.0 ±17.4 µM. It was evident that the 4 compounds showed %CI greater than 75% in all strains, except for compound LS12 in the HT-29 strain. The IC50 variation was due to the substituents present in the aromatic ring of the structure of the molecules and the cell line tested. CONCLUSION: From the initial screening carried out, the LSS4 and LSS6 derivatives stood out for presenting relevant activity in all cell lines, especially in the K562 lineage where they obtained the highest %CI (99.4±0.4 and 98.3±1.1, respectively) and the lowest IC50 values (4.6±0.6 and 3.9±0.1, respectively). These derivatives were selected for future reproduction of the MTT test, now within 48 h, in this same cell line (K562), to investigate the characteristics of the type of cell death caused by the compounds.
ACKNOWLEDGEMENT: The authors are grateful for the postgraduate scholarships Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE).
REFERENCES
[1] SUNG, H.; FERLAY, J.; SIEGEL, R.; LAVERSANNE, M.; SOERJOMATARAM, I.; JEMAL, A.; BRAY, F. Global Cancer Statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Ca: A Cancer Journal for Clinicians, [S.L.], v. 71, n. 3, p. 209-249, 2021.
[2] BERALDO, H.; GAMBINO, D. The wide pharmacological versatility of semicarbazones, thiosemicarbazones and their metal complexes. Mini Reviews in Medicinal Chemistry, v. 4, p. 31-39, 2004.
[3] OLIVEIRA, R. B.; SOUZA-FAGUNDES, E. M.; SOARES, R. P.; ANDRADE, A. A.; KRETTLI, A.; ZANI, C. L. Synthesis and antimalarial activity of semicarbazoneand thiosemicarbazone derivatives. European Journal of Medicinal Chemistry, v. 43, p. 1983-1988, 2008.
[4] REN, S.; WANG, R.; KOMATSU, K.; BONAZ-KRAUSE, P.; ZYRIANOV, Y.; MCKENNA, C.E.; LIEN, E..J. Synthesis, biological evaluation, and quantitative structure-activity relationship analysis of new Schiff bases of hydroxysemicarbazide as potential antitumor agents. Journal of Medicinal Chemistry, v 45, p. 410-419, 2002.
Comissão Organizadora
Francisco Mendonça Junior
Pascal Marchand
Teresinha Gonçalves da Silva
Isabelle Orliac-Garnier
Gerd Bruno da Rocha
Comissão Científica
Ricardo Olimpio de Moura
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