1,4-Disubstituted-5-hydroxy-3-methylpyrazoles and some derived ring systems as cytotoxic and DNA binding agents. Synthesis, in vitro biological evaluation and in silico ADME study

Autor: Mona H. Badr, Heba A. Abd El Razik
Rok vydání: 2017
Předmět:
Zdroj: Medicinal Chemistry Research. 27:442-457
ISSN: 1554-8120
1054-2523
Popis: Some novel polysubstituted pyrazoles, bipyrazoles and pyranopyrazoles, supported with various chemotherapeutically-active pharmacophores, were synthesized and biologically evaluated for their cytotoxic potential. Fifteen compounds (7–9, 12, 16, 17, 19, 21, 22, 26, 28, 30, 32, 33, and 34) exhibited variable degrees of cytotoxic activity against a panel of three cancer cell lines, among which the analogs 16, 17, 21, 26, and 34 showed a considerable broad spectrum cytotoxic potential, with special effectiveness against the colon HT29 and breast MCF7 cancer cell lines. In particular, compounds 16, 17, and 26 displayed double the activity of doxorubicin against colon carcinoma HT29 cell line, while the pyranopyrazole analog 34 was nearly equiactive with the reference cytotoxic agent. Meanwhile, the analogs 16 and 17 were nearly equipotent to doxorubicin against breast MCF7 cell line. DNA-binding activities of the most active compounds were in agreement with the obtained anticancer activity, where compounds 16, 17, 26, and 34 displayed the highest affinity. In silico calculations of molecular properties revealed that most of the active compounds comply with Lipinski’s RO5 and Veber’s criteria for good bioavailability suggesting good drug-likeness properties upon oral administration.
Databáze: OpenAIRE
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