دورية أكاديمية

Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential.

التفاصيل البيبلوغرافية
العنوان: Synthesis and evaluation of the mutagenicity of 3-alkylpyridine marine alkaloid analogues with anticancer potential.
المؤلفون: Barbosa MCS; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., de Souza Barbosa C; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., de Oliveira JT; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Moreira NCS; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., de Miranda Martins NR; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Alves Gomes GK; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Caldeira CA; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Alves E Costa ML; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil; LQTC: Laboratório de Química Teórica e Computacional, Departamento de Ciências Naturais (DCNAT), Universidade Federal de São João Del-Rei (UFSJ), Campus Dom Bosco, 36301-160, São João Del-Rei, MG, Brazil., Martins Guimarães DS; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Guimarães L; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil; LQTC: Laboratório de Química Teórica e Computacional, Departamento de Ciências Naturais (DCNAT), Universidade Federal de São João Del-Rei (UFSJ), Campus Dom Bosco, 36301-160, São João Del-Rei, MG, Brazil., Nascimento CS Jr; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil; LQTC: Laboratório de Química Teórica e Computacional, Departamento de Ciências Naturais (DCNAT), Universidade Federal de São João Del-Rei (UFSJ), Campus Dom Bosco, 36301-160, São João Del-Rei, MG, Brazil., de Pilla Varotti F; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Ribeiro Viana GH; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil., Santos FVD; Núcleo de Pesquisa em Química Biológica (NQBio), Universidade Federal de São João del Rei, Campus Centro-Oeste, Av. Sebastião Gonçalves Coelho, 400, Divinópolis, MG 35501-296, Brazil. Electronic address: fabiosantos@ufsj.edu.br.
المصدر: Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2018 Jan; Vol. 825, pp. 31-39. Date of Electronic Publication: 2017 Nov 24.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101632149 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-3592 (Electronic) Linking ISSN: 13835718 NLM ISO Abbreviation: Mutat Res Genet Toxicol Environ Mutagen Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Amsterdam : Elsevier, 1997-
مواضيع طبية MeSH: Alkaloids/*pharmacology , Antimalarials/*pharmacology , Antineoplastic Agents/*pharmacology , Pyridines/*pharmacology , Theonella/*chemistry, Alkaloids/chemical synthesis ; Alkaloids/chemistry ; Animals ; Antimalarials/chemical synthesis ; Antimalarials/chemistry ; Antineoplastic Agents/chemical synthesis ; Antineoplastic Agents/chemistry ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Comet Assay ; Humans ; Inhibitory Concentration 50 ; Micronucleus Tests ; Models, Molecular ; Plasmodium falciparum/drug effects ; Pyridines/chemical synthesis ; Pyridines/chemistry ; Structure-Activity Relationship
مستخلص: Theonella sp is an important source of biologically-active 3-alkylpyridine alkaloids (3-APAs) that has shown a wide variety of promising biological effects. In the present work, two new 3-APAs analogues were synthesized based on molecular modeling studies to act as potential antimalarial agents. These theoneladin C analogues, containing the thiocyanate group in their chemical structures, were synthesized and evaluated against Plasmodium falciparum (IC 50 values ranging from 2.3 to 5.5μM). The structural and energetic analysis demonstrated a high chemical affinity of the two analogues for their target, the heme group. However, despite the good antimalarial activity, the compounds exhibited high cytotoxicity and a lack of selectivity for human cell lines. These findings prompted us to evaluate the cytotoxicity of these compounds against human cancer cell lines. In order to better understand the mechanisms responsible for the toxicity, a variety of genotoxicity assays were performed in vitro. One of the compounds assayed presented an interesting selectivity and high toxicity to the human colon cancer cell line RKO-AS45-1. In addition, the results of the micronucleus assay, comet assay, Ames assay and annexin-V/propidium iodide staining showed that the synthetic alkaloids were able to induce chromosomal mis-segregation and trigger cell death by apoptosis. These results demonstrate that the compounds assessed herein may be promising prototypes of anticancer chemotherapeutic agents.
(Copyright © 2017 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Aneugen; Antimalarial; Genotoxicity; Thiocyanate group
المشرفين على المادة: 0 (Alkaloids)
0 (Antimalarials)
0 (Antineoplastic Agents)
0 (Pyridines)
تواريخ الأحداث: Date Created: 20180109 Date Completed: 20190603 Latest Revision: 20190603
رمز التحديث: 20221213
DOI: 10.1016/j.mrgentox.2017.11.006
PMID: 29307373
قاعدة البيانات: MEDLINE