1. Synthetic enamine naphthoquinone derived from lawsone as cytotoxic agents assessed by in vitro and in silico evaluations
- Author
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Pedro Mikael da Silva Costa, Sandro J. Greco, Bárbara C. Lemos, Rodolfo G. Fiorot, Fátima de Cássia Evangelista de Oliveira, Regina Westphal, Anne Caroline Candido Gomes, José Walkimar de M. Carneiro, Celina de Jesus Guimarães, Cláudia Campos Pessoa, and Eclair Venturini Filho
- Subjects
Cell Survival ,In silico ,Clinical Biochemistry ,Pharmaceutical Science ,Antineoplastic Agents ,Biochemistry ,Lawsone ,Enamine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Cell Line, Tumor ,Drug Discovery ,Humans ,Structure–activity relationship ,MTT assay ,Amines ,Picolinic Acids ,Molecular Biology ,Cell Proliferation ,Dose-Response Relationship, Drug ,Molecular Structure ,Cytotoxins ,Organic Chemistry ,Quinoline ,Combinatorial chemistry ,Naphthoquinone ,chemistry ,Docking (molecular) ,Quinolines ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Naphthoquinones - 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.
- Published
- 2021
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