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- Title
Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.
- Authors
dos Santos Maia, Mayara; Raimundo e Silva, Joanda Paolla; de Lima Nunes, Thaís Amanda; Saraiva de Sousa, Julyanne Maria; Soares Rodrigues, Gabriela Cristina; Messias Monteiro, Alex France; Fechine Tavares, Josean; da Franca Rodrigues, Klinger Antonio; B. Mendonça-Junior, Francisco Jaime; Scotti, Luciana; Scotti, Marcus Tullius
- Abstract
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 Leishmaniamajor 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 Justiciaaequilabris (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 IC50 value of 5.39 µM and IC50 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.
- Subjects
LIGNANS; COMPUTER-assisted drug design; NEOLIGNANS; DRUG design; DRUG resistance; DRUG development; LEISHMANIASIS
- Publication
Molecules, 2020, Vol 25, Issue 10, p2281
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25102281