| Autor: |
Maia MDS; Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Silva JPRE; Multi-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Nunes TAL; Infectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, Brazil., Sousa JMS; Infectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, Brazil., Rodrigues GCS; Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Monteiro AFM; Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Tavares JF; Multi-User Characterization and Analysis Laboratory, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Rodrigues KADF; Infectious Diseases Laboratory, Federal University of Parnaíba Delta, São Benedito, Parnaíba-PI 64202-020, Brazil., Mendonça-Junior FJB; Laboratory of Synthesis and Drug Delivery, State University of Paraíba, João Pessoa-PB 58071-160, Brazil., Scotti L; Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil., Scotti MT; Laboratory of Cheminformatics, Program of Natural and Synthetic Bioactive Products (PgPNSB), Health Sciences Center, Federal University of Paraíba, João Pessoa-PB 58051-900, Brazil. |
| Abstrakt: |
Leishmaniasis is endemic in at least 98 countries. Due to the high toxicity and resistance associated with the drugs, we chose lignans as an alternative, due to their favorable properties of absorption, distribution, metabolism, excretion, and toxicity (ADMET). To investigate their leishmanicidal potential, the biological activities of a set of 160 lignans were predicted using predictive models that were built using data for Leishmania major and L. (Viannia) braziliensis . A combined analysis, based on ligand and structure, and several other computational approaches were used. The results showed that the combined analysis was able to select 11 lignans with potential activity against L. major and 21 lignans against L. braziliensis , with multitargeting effects and low or no toxicity. Of these compounds, four were isolated from the species Justicia aequilabris (Nees) Lindau. All of the identified compounds were able to inhibit the growth of L. braziliensis promastigotes, with the most active compound, ( 159 ) epipinoresinol-4- O -β-d-glucopyranoside, presenting an IC 50 value of 5.39 µM and IC 50 value of 36.51 µM for L. major . Our findings indicated the potential of computer-aided drug design and development and demonstrated that lignans represent promising prototype compounds for the development of multitarget drugs against leishmaniasis. |
