Synthesis of pyrazole-substituted chromene analogues with selective anti-leukemic activity
- Autores: Madhu G.1, Sudhakar M.1, Santosh Kumar K.1, Rajashekher Reddy G.1, Sravani A.2, Ramakrishna K.2, Prasad Rao C.1
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Afiliações:
- Natural Products Laboratory, Department of Chemistry
- Molecular Medicine and Therapeutics Laboratory, Centre for Plant Molecular Biology
- Edição: Volume 87, Nº 10 (2017)
- Páginas: 2421-2428
- Seção: Article
- URL: https://journals.rcsi.science/1070-3632/article/view/221466
- DOI: https://doi.org/10.1134/S1070363217100243
- ID: 221466
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Resumo
We report design and synthesis of a series of flavanone/chromene derivatives containing pyrazoles 6a–6h and 8a–8e with potent anti-leukemic activity. Anti-leukemic activity of novel flavanone derivatives was tested using the K562 cell line. The parental flavanone was selected as the reference compound in identification of analogues with superior anti-leukemic activity. More than two-thirds of the derivatives displayed higher activity than the initial flavanone. Positions of substituents that promoted anti-leukemic activity were identified on both the chromene and pyrazole fragments. Compounds 6b and 6c showed the highest activity against K562 cell line, with IC50 values 3.0 and 0.5 μM respectively. Notably, compounds 6b and 6c displayed very high selectivity in inhibition of leukemic cells (K562) but not of healthy HEK293 cells or solid cancer cell lines HeLa, MCF7 and BT474. Moreover, both the 6b and 6c compounds were predicted to have good ADME properties.
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Sobre autores
G. Madhu
Natural Products Laboratory, Department of Chemistry
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
M. Sudhakar
Natural Products Laboratory, Department of Chemistry
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
K. Santosh Kumar
Natural Products Laboratory, Department of Chemistry
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
G. Rajashekher Reddy
Natural Products Laboratory, Department of Chemistry
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
A. Sravani
Molecular Medicine and Therapeutics Laboratory, Centre for Plant Molecular Biology
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
K. Ramakrishna
Molecular Medicine and Therapeutics Laboratory, Centre for Plant Molecular Biology
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
Ch. Prasad Rao
Natural Products Laboratory, Department of Chemistry
Autor responsável pela correspondência
Email: prasadraoou@yahoo.com
Índia, Hyderabad, Telangana, 500007
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