Design,synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| |
| Institution: | 1. Medicinal Chemistry Laboratory, Pharmacy and Nursing School, Federal University of Alagoas, Maceio, Brazil;2. Cell Biology Laboratory, Federal University of Alagoas, Maceio, Brazil;3. Biochemistry and Immunology Department, Biological Sciences Institute, Federal University of Minas Gerais, Belo Horizonte, Brazil;4. Inorganic Synthesis and Crystallography Laboratory, Institute of Chemistry, University of Brasilia, Federal District, Brazil;5. Tissue Engineering and Immunopharmacology Laboratory, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil;6. Skaggs School of Pharmacy and Pharmaceutical Sciences, California, San Diego La Jolla, United States;7. Laboratory of Drug Synthesis and Delivery, Biological Sciences Department, State University of Paraiba, Campus V, João Pessoa, Brazil;8. Drug Design and Synthesis Laboratory, National Science and Technology Institute for Pharmaceutical Innovation, Federal University of Pernambuco, Recife, Brazil;9. Catalysis and Chemical Reactivity Group (GCaR), Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceio, 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 6.03 μM. The 8c derivative showed the highest potency against cruzain (IC50 = 2.4 μM). 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 = ?7.39 kcal·mol?1) indicates interaction (via dipole–dipole) between the hybridized sulfur sp3 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 Chagas disease |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
