Computer-Assisted Design of Thiophene-Indole Hybrids as Leishmanial Agents.

Autor:	Félix MB; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, Joao Pessoa- PB 58051-900, Brazil., de Araújo RSA; Laboratory of Synthesis and Drug Delivery, State University of Paraiba, Joao Pessoa-PB 58071-160, Brazil., Barros RPC; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, Joao Pessoa- PB 58051-900, Brazil., de Simone CA; Departamento de Fisica e Informatica, Instituto de Fisica de Sao Carlos, Universidade de Sao Paulo - USP, 13560-970 Sao Carlos-SP, Brazil., Rodrigues RRL; Laboratorio de Doencas Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaiba, 64202-020 Parnaiba, PI, Brazil., de Lima Nunes TA; Laboratorio de Doencas Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaiba, 64202-020 Parnaiba, PI, Brazil., da Franca Rodrigues KA; Laboratorio de Doencas Infecciosas, Campus Ministro Reis Velloso, Universidade Federal do Delta do Parnaiba, 64202-020 Parnaiba, PI, Brazil., Junior FJBM; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, Joao Pessoa- PB 58051-900, Brazil., Muratov E; Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States., Scotti L; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, Joao Pessoa- PB 58051-900, Brazil., Scotti MT; Post-Graduation Program in Natural and Synthetic Bioactive Products, Federal University of Paraiba, Joao Pessoa- PB 58051-900, Brazil.
Jazyk:	angličtina
Zdroj:	Current topics in medicinal chemistry [Curr Top Med Chem] 2020; Vol. 20 (19), pp. 1704-1719.
DOI:	10.2174/1568026620666200616142120
Abstrakt:	Background: Chemoinformatics has several applications in the field of drug design, helping to identify new compounds against a range of ailments. Among these are Leishmaniasis, effective treatments for which are currently limited. Objective: To construct new indole 2-aminothiophene molecules using computational tools and to test their effectiveness against Leishmania amazonensis (sp.). Methods: Based on the chemical structure of thiophene-indol hybrids, we built regression models and performed molecular docking, and used these data as bases for design of 92 new molecules with predicted pIC50 and molecular docking. Among these, six compounds were selected for the synthesis and to perform biological assays (leishmanicidal activity and cytotoxicity). Results: The prediction models and docking allowed inference of characteristics that could have positive influences on the leishmanicidal activity of the planned compounds. Six compounds were synthesized, one-third of which showed promising antileishmanial activities, with IC50 ranging from 2.16 and 2.97 μM (against promastigote forms) and 0.9 and 1.71 μM (against amastigote forms), with selectivity indexes (SI) of 52 and 75. Conclusion: These results demonstrate the ability of Quantitative Structure-Activity Relationship (QSAR)-based rational drug design to predict molecules with promising leishmanicidal potential, and confirming the potential of thiophene-indole hybrids as potential new leishmanial agents. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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