Synthesis of New N1Arylpiperazine Substituted Xanthine Derivatives and Evaluation of their Antioxidant and Cytotoxic Effects.
Aralkylpiperazine
QSAR
antioxidant effect
cytotoxicity
leukemia cell SKW-3
theobromine.
Journal
Anti-cancer agents in medicinal chemistry
ISSN: 1875-5992
Titre abrégé: Anticancer Agents Med Chem
Pays: Netherlands
ID NLM: 101265649
Informations de publication
Date de publication:
2019
2019
Historique:
received:
25
06
2018
revised:
31
08
2018
accepted:
09
01
2019
pubmed:
23
1
2019
medline:
28
2
2020
entrez:
23
1
2019
Statut:
ppublish
Résumé
Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods - DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.
Sections du résumé
BACKGROUND
Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities.
METHODS
The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods - DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines.
RESULTS
A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn.
CONCLUSION
The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.
Identifiants
pubmed: 30666917
pii: ACAMC-EPUB-95985
doi: 10.2174/1871520619666190121155651
doi:
Substances chimiques
Antineoplastic Agents
0
Antioxidants
0
Piperazines
0
Xanthines
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
528-537Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.