In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to reveal their in vitro inhibition activities. Molecular modeling studies were performed to acquire data about the binding modes of the inhibitors. Three sirtuin inhibitors were subjected to cellular studies, and all of them showed an increase in acetylation of Lys382 of p53 after DNA damage. Furthermore, two of the compounds were able to inhibit both A549 lung carcinoma and MCF-7 breast carcinoma cell growth in micromolar concentration with the ability to arrest cancer cell cycle in the G1 phase.

Screen of pseudopeptidic inhibitors of human sirtuins 1-3: Two lead compounds with antiproliferative effects in cancer cells / Mellini, Paolo; Kokkola, Tarja; Suuronen, Tiina; Salo, Heikki S.; Tolvanen, Laura; Mai, Antonello; Lahtela Kakkonen, Maija; Jarho, Elina M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 56:17(2013), pp. 6681-6695. [10.1021/jm400438k]

Screen of pseudopeptidic inhibitors of human sirtuins 1-3: Two lead compounds with antiproliferative effects in cancer cells

MAI, Antonello;
2013

Abstract

In the past few years sirtuins have gained growing attention for their involvement in many biological processes such as cellular metabolism, apoptosis, aging and inflammation. In this contribution, we report the synthesis of a library of thioacetylated pseudopeptides that were screened against human sirtuins 1-3 to reveal their in vitro inhibition activities. Molecular modeling studies were performed to acquire data about the binding modes of the inhibitors. Three sirtuin inhibitors were subjected to cellular studies, and all of them showed an increase in acetylation of Lys382 of p53 after DNA damage. Furthermore, two of the compounds were able to inhibit both A549 lung carcinoma and MCF-7 breast carcinoma cell growth in micromolar concentration with the ability to arrest cancer cell cycle in the G1 phase.
2013
Cell Line, Tumor; Cell Proliferation; Humans; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Docking Simulation; Peptides; Sirtuins; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Molecular Medicine; Drug Discovery3003 Pharmaceutical Science
01 Pubblicazione su rivista::01a Articolo in rivista
Screen of pseudopeptidic inhibitors of human sirtuins 1-3: Two lead compounds with antiproliferative effects in cancer cells / Mellini, Paolo; Kokkola, Tarja; Suuronen, Tiina; Salo, Heikki S.; Tolvanen, Laura; Mai, Antonello; Lahtela Kakkonen, Maija; Jarho, Elina M.. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - 56:17(2013), pp. 6681-6695. [10.1021/jm400438k]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/884236
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