Cytotoxic Activity and DNA Binding Property of New Aminopyrimidine Derivatives

Author(s): Hamidreza Akrami, Bibi Fatemeh Mirjalili, Omidreza Firuzi, Azadeh Hekmat, Ali Akbar Saboury, Ramin Miri, Omid Sabzevari, Morteza Pirali-Hamedani, Fereshteh Jeivad, Setareh Moghimi, Saeed Emami, Alireza Foroumadi*, Mehdi Khoobi*.

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 5 , 2020

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Graphical Abstract:


Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity.

Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines was evaluated using MTT assay. The interaction of the most promising compound with calf-thymus DNA was also studied using spectrometric titrations and Circular Dichroism (CD) spectroscopy.

Results: Most compounds showed promising activity against tested cell lines. Among them, 2,4- dimethoxyanilino derivative 6g exhibited the best profile of activity against tested cell lines (IC50s = 1.6-6.1 μM) with no toxicity against NIH3T3 normal cell (IC50 >200 μM). The spectrometric studies exhibited that compound 6g binds to DNA strongly and may change DNA conformation significantly, presumably via a groove binding mechanism.

Conclusion: The results of this study suggest that the prototype compound 6g can be considered as a novel lead compound for the design and discovery of novel anticancer agents.

Keywords: Anti-cancer activity, benzo[f]chromene, polycyclic compounds, multi-component reactions, DNA-binding, aminopyrimidine derivatives.

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Article Details

Year: 2020
Page: [640 - 654]
Pages: 15
DOI: 10.2174/1570180816666190712102119
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