2. Academic Validation
  3. Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations

Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations

  • Bioorg Med Chem Lett. 2021 Dec 1:53:128419. doi: 10.1016/j.bmcl.2021.128419.
Bárbara C Lemos 1,  Regina Westphal 1,  Eclair Venturini Filho 1,  Rodolfo G Fiorot 2,  José Walkimar M Carneiro 2,  Anne Caroline C Gomes 3,  Celina J Guimarães 4,  Fátima C E de Oliveira 5,  Pedro Mikael S Costa 5,  Claudia Pessoa 5,  Sandro J Greco 6
Affiliations

Affiliations

  • 1 Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • 2 Chemistry Institute, Federal Fluminense University, Outeiro de São João Batista, 24020-141 Niteroi, RJ, Brazil.
  • 3 Faculty of Pharmacy, Federal Institute of Rio de Janeiro, Campus Realengo, Rio de Janeiro CEP.: 21715-000, Brazil.
  • 4 Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará., Fortaleza, Ceará CEP.: 60430-275, Brazil; Pharmacy Sector, Foundation of Oncology Control of the state of Amazonas, Manaus, Amazonas CEP.: 69040-010, Brazil.
  • 5 Pharmacy Sector, Foundation of Oncology Control of the state of Amazonas, Manaus, Amazonas CEP.: 69040-010, Brazil.
  • 6 Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil. Electronic address: grecosj@outlook.com.
PMID: 34715305 DOI: 10.1016/j.bmcl.2021.128419
Abstract

We synthesized ten enamine naphthoquinones with yields ranging from 43 to 76%. These compounds were screened for their in vitro antiproliferative activities by MTT assay against four types of human Cancer cell lines: HCT116, PC3, HL60 and SNB19. The naphthoquinones bearing the picolylamine (7) and quinoline (12) moieties were the most actives (IC50 < 24 μM for all the cell lines), which were comparable or better to the values obtained for the control drugs. In silico evaluations allowed us to develop a qualitative Structure-Activity Relationship which suggest that electrostatic features, particularly the C2-C3 internuclear repulsion and the molecular dipole moment, relate to the biological response. Furthermore, Molecular Docking simulations indicate that the synthetic compounds have the potential to act as Anticancer molecules by inhibiting topoisomerase-II and Thymidylate Synthase.

Keywords

Antiproliferative activity; Docking; Enamine naphthoquinone; Structure/activity relationship.

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