The introduction of a methylenthiol group at position7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.
Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation / M.S. Christodoulou, F. Zunino, V. Zuco, S. Borrelli, D. Comi, G. Fontana, M. Martinelli, J.B. Lorens, L. Evensen, M. Sironi, S. Pieraccini, L. Dalla Via, O.M. Gia, D. Passarella. - In: CHEMMEDCHEM. - ISSN 1860-7179. - 7:12(2012), pp. 2134-2143. [10.1002/cmdc.201200322]
Camptothecin-7-yl-methanthiole: semisynthesis and biological evaluation
M.S. Christodoulou;S. Borrelli;D. Comi;M. Sironi;S. Pieraccini;D. PassarellaUltimo
2012
Abstract
The introduction of a methylenthiol group at position7 of camptothecin was carried out in four steps. This preparation also yielded the corresponding disulfide, which behaves as a prodrug due to its reactivity with glutathione. Assessment of their antiproliferative activities, investigations of their mechanism of action, and molecular modeling analysis indicated that the 7-modified camptothecin derivatives described herein maintain the biological activity and drug-target interactions of the parent compound.
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