Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives

Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives Publisher

Akrami H^{1, 2} ; Mirjalili BF² ; Firuzi O³ ; Hekmat A⁴ ; Saboury AA⁵ ; Miri R³ ; Sabzevari O⁶ ; Piralihamedani M⁷ ; Jeivad F⁶ ; Moghimi S¹ ; Emami S⁸ ; Foroumadi A⁷ ; Khoobi M^{1, 7}

Show Affiliations

1. The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
2. Department of Chemistry, College of Science, Yazd University, PO Box 8915813149, Yazd, Iran
3. Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
4. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
5. Institute of Biochemistry and Biophysics, University of Teh-ran, Tehran, Iran
6. Toxicology and Poisoning Research Centre, Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
7. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
8. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran

Source: Letters in Drug Design and Discovery Published:2020

Abstract

Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved an-ticancer activity. Method: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as an-ticancer 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 Dichro-ism (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 spectro-metric 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. © 2020 Bentham Science Publishers.

Related Docs

1. Facile Synthesis and Antiproliferative Activity of 7H-Benzo[7,8]Chromeno[2,3-D]Pyrimidin-8-Amines, European Journal of Medicinal Chemistry (2017)

2. Synthesis and Biological Evaluation of New Coumarins Bearing 2,4-Diaminothiazole-5-Carbonyl Moiety, European Journal of Medicinal Chemistry (2018)

3. 6-Cinnamoyl-4-Arylaminothienopyrimidines As Highly Potent Cytotoxic Agents: Design, Synthesis and Structure-Activity Relationship Studies, European Journal of Medicinal Chemistry (2020)

4. Synthesis and Biological Evaluation of 4-Amino-5-Cinnamoylthiazoles As Chalcone-Like Anticancer Agents, European Journal of Medicinal Chemistry (2018)

Experts (# of related papers)

View all Related Experts

Alireza Foroumadi (4)

Loghman Firoozpour (2)

Style	Citing Format
MLA	Akrami H, et al.. "Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives." Letters in Drug Design and Discovery, vol. 17, no. 5, 2020, pp. 638-652.
APA	Akrami H, Mirjalili BF, Firuzi O, Hekmat A, Saboury AA, Miri R, Sabzevari O, Piralihamedani M, Jeivad F, Moghimi S, Emami S, Foroumadi A, Khoobi M (2020). Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives. Letters in Drug Design and Discovery, 17(5), 638-652.
Chicago	Akrami H, Mirjalili BF, Firuzi O, Hekmat A, Saboury AA, Miri R, Sabzevari O, et al.. "Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives." Letters in Drug Design and Discovery 17, no. 5 (2020): 638-652.
Harvard	Akrami H et al. (2020) 'Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives', Letters in Drug Design and Discovery, 17(5), pp. 638-652.
Vancouver	Akrami H, Mirjalili BF, Firuzi O, Hekmat A, Saboury AA, Miri R, et al.. Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives. Letters in Drug Design and Discovery. 2020;17(5):638-652.
BibTex	@article{ author = {Akrami H and Mirjalili BF and Firuzi O and Hekmat A and Saboury AA and Miri R and Sabzevari O and Piralihamedani M and Jeivad F and Moghimi S and Emami S and Foroumadi A and Khoobi M}, title = {Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives}, journal = {Letters in Drug Design and Discovery}, volume = {17}, number = {5}, pages = {638-652}, year = {2020} }
RIS	TY - JOUR AU - Akrami H AU - Mirjalili BF AU - Firuzi O AU - Hekmat A AU - Saboury AA AU - Miri R AU - Sabzevari O AU - Piralihamedani M AU - Jeivad F AU - Moghimi S AU - Emami S AU - Foroumadi A AU - Khoobi M TI - Cytotoxic Activity and Dna Binding Property of New Aminopyrimidine Derivatives JO - Letters in Drug Design and Discovery VL - 17 IS - 5 SP - 638 EP - 652 PY - 2020 ER -

Science Communicator Platform

Authors

Authors Affiliations

Abstract