TY - JOUR
T1 - Antineoplastic Agents. 607. Emetine Auristatins
AU - Pettit, George R.
AU - Melody, Noeleen
AU - Chapuis, Jean Charles
N1 - Funding Information:
With appreciation, we acknowledge and thank for financial support the J.W. Kieckhefer Foundation and the Margaret T. Morris Foundation.
Publisher Copyright:
© 2020 American Chemical Society and American Society of Pharmacognosy.
PY - 2020/5/22
Y1 - 2020/5/22
N2 - The remarkable biological activity of the dolastatin 10 structural modifications quinstatins and isoquinstatins prompted further investigation into drug hybrids containing biologically active isoquinoline moieties. In this study, the isoquinoline alkaloid emetine was selected as one of the structural domains of a hybrid molecule. That was accomplished by covalently bonding the Dov-Val-Dil-Dap peptide sequence of dolastatin 10 peptide at the N-2′ secondary amine of emetine. Three new hybrids were synthesized, 5, 9, and 10. Comparison of the biological activity of these new peptide-emetine analogues with emetine showed complete retention of activity for 5 and a 10-fold decrease for hybrids 9 and 10. The result was surprising, as the activity of emetine is usually lost or greatly reduced when substituted at the N-2′ position.
AB - The remarkable biological activity of the dolastatin 10 structural modifications quinstatins and isoquinstatins prompted further investigation into drug hybrids containing biologically active isoquinoline moieties. In this study, the isoquinoline alkaloid emetine was selected as one of the structural domains of a hybrid molecule. That was accomplished by covalently bonding the Dov-Val-Dil-Dap peptide sequence of dolastatin 10 peptide at the N-2′ secondary amine of emetine. Three new hybrids were synthesized, 5, 9, and 10. Comparison of the biological activity of these new peptide-emetine analogues with emetine showed complete retention of activity for 5 and a 10-fold decrease for hybrids 9 and 10. The result was surprising, as the activity of emetine is usually lost or greatly reduced when substituted at the N-2′ position.
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U2 - 10.1021/acs.jnatprod.0c00031
DO - 10.1021/acs.jnatprod.0c00031
M3 - Article
C2 - 32323990
AN - SCOPUS:85084236369
VL - 83
SP - 1571
EP - 1576
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 5
ER -