In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway.

Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets / Maslivetc, Vladimir; Laguera, Breana; Chandra, Sunena; Dasari, Ramesh; Olivier, Wesley J; Smith, Jason A; Bissember, Alex C; Masi, Marco; Evidente, Antonio; Mathieu, Veronique; Kornienko, Alexander. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 22:20(2021), p. 11256. [10.3390/ijms222011256]

Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets

Masi, Marco
Membro del Collaboration Group
;
2021

Abstract

In a search of small molecules active against apoptosis-resistant cancer cells, including glioma, melanoma, and non-small cell lung cancer, we previously prepared α,β- and γ,δ-unsaturated ester analogues of polygodial and ophiobolin A, compounds capable of pyrrolylation of primary amines and demonstrating double-digit micromolar antiproliferative potencies in cancer cells. In the current work, we synthesized dimeric and trimeric variants of such compounds in an effort to discover compounds that could crosslink biological primary amine containing targets. We showed that such compounds retain the pyrrolylation ability and possess enhanced single-digit micromolar potencies toward apoptosis-resistant cancer cells. Target identification studies of these interesting compounds are underway.
2021
Polygodial and Ophiobolin A Analogues for Covalent Crosslinking of Anticancer Targets / Maslivetc, Vladimir; Laguera, Breana; Chandra, Sunena; Dasari, Ramesh; Olivier, Wesley J; Smith, Jason A; Bissember, Alex C; Masi, Marco; Evidente, Antonio; Mathieu, Veronique; Kornienko, Alexander. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 22:20(2021), p. 11256. [10.3390/ijms222011256]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/904343
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