Discovery of steroidal lactam conjugates of POPAM-NH2 with potent anticancer activity
| Autor: | Maria Voura, Elena Geromichalou, Dimitrios T Trafalis, Panagiotis Dalezis, Margarita Grammatikopoulou, C. Gabriel, Sofia Sagredou, Vasiliki Sarli, Eleni Sflakidou |
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| Rok vydání: | 2020 |
| Předmět: |
Pharmacology
Melphalan 0303 health sciences Prednimustine Prodrug Nitrogen mustard 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry 030220 oncology & carcinogenesis Drug Discovery Lactam medicine Molecular Medicine Estramustine 030304 developmental biology Conjugate medicine.drug |
| Zdroj: | Future Medicinal Chemistry. 12:19-35 |
| ISSN: | 1756-8927 1756-8919 |
| Popis: | Aim: Steroidal prodrugs of nitrogen mustards such as estramustine and prednimustine have proven effective anticancer agents in clinical use since the 1970s. In this work, we aimed to develop steroidal prodrugs of the novel nitrogen mustard POPAM-NH2. POPAM-NH2 is a melphalan analogue that was coupled with three different steroidal lactams. Methodology: The new conjugates were preclinically tested for anticancer activity against nine human and one rodent cancer experimental models, in vitro and in vivo. Results & conclusion: All the steroidal alkylators showed high antitumor activity, in vitro and in vivo, in the experimental systems tested. Moreover, these hybrid compounds showed by far superior anticancer activity compared with the alkylating agents, melphalan and POPAM-NH2. |
| Databáze: | OpenAIRE |
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