TY  - JOUR
AU  - Boto, A.
AU  - Miguélez, J.
AU  - Marín, R.
AU  - Díaz, M.
T1  - Synthesis of indolizidinone analogues of cytotoxic alkaloids: Monocyclic precursors are also active
LA  - eng
PY  - 2012
SP  - 3402
EP  - 3407
T2  - Bioorganic and Medicinal Chemistry Letters
SN  - 0960-894X
VL  - 22
IS  - 10
AB  - Readily available proline derivatives can be transformed in just two steps into analogues of cytotoxic phenanthroindolizidine alkaloids. The key step uses a sequential radical scission-oxidation-alkylation process, which yields 2-substituted pyrrolidine amides. A second process effects the cyclization to give the desired alkaloid analogues, which possess an indolizidine core. The major and minor isomers (dr 3:2 to 3:1) can be easily separated, allowing their use to study structure-activity relationships (SAR). The process is versatile and allows the introduction of aryl and heteroaryl groups (including biphenyl, halogenated phenyl, and pyrrole rings). Some of these alkaloid analogues displayed a selective cytotoxic activity against tumorogenic human neuronal and mammary cancer cells, and one derivative caused around 80% cell death in both tumor lines at micromolar doses. The cytotoxicity of some monocyclic precursors was also studied, being comparable or superior to the bicyclic derivatives. © 2012 Elsevier Ltd. All rights reserved.
DO  - 10.1016/J.BMCL.2012.03.109
UR  - https://portalciencia.ull.es/documentos/5e39b7b62999523aa92715b2
DP  - Dialnet - Portal de la Investigación
ER  -