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Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.

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 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-?-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.

SUBMITTER: Maia MDS

PROVIDER: S-EPMC7288103 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.

Maia Mayara Dos Santos MDS Silva Joanda Paolla Raimundo E JPRE Nunes Thaís Amanda de Lima TAL Sousa Julyanne Maria Saraiva de JMS Rodrigues Gabriela Cristina Soares GCS Monteiro Alex France Messias AFM Tavares Josean Fechine JF Rodrigues Klinger Antonio da Franca KADF Mendonça-Junior Francisco Jaime B FJB Scotti Luciana L Scotti Marcus Tullius MT

Molecules (Basel, Switzerland) 20200512 10

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 ...[more]

PMID: 32408657

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Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.

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Virtual Screening and the In Vitro Assessment of the Antileishmanial Activity of Lignans.

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