Antileishmanial activity of Riparin structural analogs of Aniba riparia: Biological evaluation, in silico Adme-Tox, and molecular docking

Kayo Alves Figueiredo; Rayla Kelly Magalhães Costa; Jefferson Almeida Rocha; Stanley Juan Chavez Gutierrez; Ricardo Martins Ramos; Michel Muálem de Moraes Alves; Fernando Aécio de Amorim Carvalho; André Luis Menezes Carvalho; Francisco das Chagas Alves Lima

doi:10.1016/j.exppara.2022.108257

Antileishmanial activity of Riparin structural analogs of Aniba riparia: Biological evaluation, in silico Adme-Tox, and molecular docking

Exp Parasitol. 2022 May-Jun:236-237:108257. doi: 10.1016/j.exppara.2022.108257. Epub 2022 Apr 6.

Authors

Kayo Alves Figueiredo¹, Rayla Kelly Magalhães Costa², Jefferson Almeida Rocha³, Stanley Juan Chavez Gutierrez⁴, Ricardo Martins Ramos⁵, Michel Muálem de Moraes Alves⁶, Fernando Aécio de Amorim Carvalho⁶, André Luis Menezes Carvalho⁷, Francisco das Chagas Alves Lima⁸

Affiliations

¹ Departamento de Saúde, Campus Teresina Central, Instituto Federal do Piauí, IFPI, Teresina, PI, Brazil; Universidade Federal do Piauí, UFPI, Programa de Pós-graduação em Biotecnologia (RENORBIO), Teresina, PI, Brazil; Laboratório de Quântica Computacional & Planejamento de Fármaco, Universidade Estadual do Piauí, UESPI, Teresina, PI, Brazil. Electronic address: kayofigueiredo@gmail.com.
² Laboratório de Quântica Computacional & Planejamento de Fármaco, Universidade Estadual do Piauí, UESPI, Teresina, PI, Brazil.
³ Laboratório de Quântica Computacional & Planejamento de Fármaco, Universidade Estadual do Piauí, UESPI, Teresina, PI, Brazil; Research Group in Natural Sciences and Biotechnology, Federal University of Maranhão, CIENATEC/UFMA, Grajau, MA, Brazil.
⁴ Curso de Farmácia, Universidade Federal do Piauí, UFPI, Teresina, PI, Brazil.
⁵ Research Laboratory in Information Systems, Department of Information, Environment, Health and Food Production, Federal Institute of Piauí, LAPESI/IFPI, Teresina, PI, Brazil.
⁶ Núcleo de Pesquisa em Plantas Medicinais, Universidade Federal do Piauí, UFPI, Teresina, PI, Brazil.
⁷ Programa de Pós-graduação em Ciências Farmacêuticas, Programa de Pós-graduação em Odontologia, Universidade Federal do Piauí, UFPI, Teresina/PI, Brazil.
⁸ Universidade Federal do Piauí, UFPI, Programa de Pós-graduação em Biotecnologia (RENORBIO), Teresina, PI, Brazil; Laboratório de Quântica Computacional & Planejamento de Fármaco, Universidade Estadual do Piauí, UESPI, Teresina, PI, Brazil.

PMID: 35398101
DOI: 10.1016/j.exppara.2022.108257

Abstract

We performed a biological evaluation of antileishmanial activity, in silico ADME-Tox profile, and molecular docking of riparins A-F. The antileishmanial activity was evaluated in Leishmania major promastigotes, whereas the cytotoxic activity was tested on murine macrophages. Computational parameters were predicted by in silico analysis. Molecular docking was performed with 18 L. major molecular targets. Riparins, especially RipC and RipE, showed cytotoxic activity in vitro toward L. major promastigotes and a high selectivity index. Riparins showed small differences in their physicochemical properties, such as polarity and aqueous solubility. LogP was an important parameter for the differences in the antileishmanial activity between the molecules. In molecular docking, the ligands displayed Ki < 1 μM for LmNMT and LmLEI. Significant molecular interactions were observed with residues from the active site and adjacent regions of such enzymes. Thus, riparins have the potential for application in antileishmanial therapy.

Keywords: Aniba riparia; Antileishmanial activity; Riparin.

MeSH terms

Animals
Antiprotozoal Agents* / chemistry
Antiprotozoal Agents* / toxicity
Leishmania major*
Ligands
Macrophages
Mice
Molecular Docking Simulation

Substances

Antiprotozoal Agents
Ligands