Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/18097
Title: Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi
Authors: Silva Júnior, E F
Silva, E P S
França, P H B
Silva, J P N
Barreto, E O
Silva, E B
Ferreira, R S
Gatto, C C
Moreira, Diogo Rodrigo Magalhães
Siqueira Neto, J L
Mendonça Júnior, F J B
Lima, M C A
Bortoluzzi, J H
Scotti, M T
Scotti, L
Meneghetti, M R
Aquino, T M
Araújo Júnior, J X
Affilliation: Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil
Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil
Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil
Federal University of Alagoas. Cell Biology Laboratory. Maceio, AL, Brazil
Federal University of Alagoas. Cell Biology Laboratory. Maceio, AL, Brazil
Federal University of Minas Gerais. Biological Sciences Institute. Biochemistry and Immunology Department. Minas Gerais, BH, Brazil
Federal University of Minas Gerais. Biological Sciences Institute. Biochemistry and Immunology Department. Minas Gerais, BH, Brazil
University of Brasilia. Institute of Chemistry. Inorganic Synthesis and Crystallography Laboratory. Brasília, DF, Brazil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil
Skaggs School of Pharmacy and Pharmaceutical Sciences. California, San Diego La Jolla, US
Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil
Federal University of Pernambuco. National Science and Technology Institute for Pharmaceutical Innovation. Drug Design and Synthesis Laboratory. Recife, PE, Brazil
Federal University of Alagoas. Institute of Chemistry and Biotechnology. Catalysis and Chemical Reactivity Group (GCaR). Maceio, AL, Brazil
Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil
Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil
Federal University of Alagoas. Institute of Chemistry and Biotechnology. Catalysis and Chemical Reactivity Group (GCaR). Maceio, AL, Brazil
Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil
Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil
Abstract: In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03μM. The 8c derivative showed the highest potency against cruzain (IC50=2.4μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb=-7.39kcal·mol(-1)) indicates interaction (via dipole-dipole) between the hybridized sulfur sp(3) atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.
Keywords: Thiophene
Thiazolidine
Docking
T. cruzi
Chagas disease
keywords: Tiofeno
Tiazolidina
T. cruzi
Doença de Chagas
Issue Date: 2016
Publisher: Elsevier
Citation: SILVA JUNIOR, E. F. et al. Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 24, p. 4228–4240, 2016.
DOI: 10.1016/j.bmc.2016.07.013
ISSN: 0968-0896
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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