期刊
JOURNAL OF CHEMICAL INFORMATION AND MODELING
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jcim.2c00559
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资金
- La Sapienza University of Rome
- Italian MIUR (Ministero dell'Istru-zione, dell'Universita e della Ricerca)
- Dipartimenti di Eccellenza-L [232/2016]
- AIRC [IG 25833]
- Istituto Pasteur-Fondazione Cenci-Bolognetti
- AFM-Telethon [21025]
- RFO grant of the Alma Mater Studiorum-University of Bologna
- Wakunaga Pharmaceutical Co. Ltd . (Japan)
Polyamines play important roles in regulating cell growth, proliferation, and death. Accumulated polyamines can be utilized as a strategy to inhibit tumor progression. This study focuses on the design and synthesis of spermine analogues, and explores their interaction with enzyme BSAO to understand the biochemical kinetics. By developing three-dimensional quantitative structure-activity relationship models, this study provides a basis for future design and synthesis of polyamine BSAO substrates for oxidative stress-induced chemotherapy.
Natural polyamines (PAs) are key players in cellular homeostasis by regulating cell growth and proliferation. Several observations highlight that PAs are also implicated in pathways regulating cell death. Indeed, the PA accumulation cytotoxic effect, maximized with the use of bovine serum amine oxidase (BSAO) enzyme, represents a valuable strategy against tumor progression. In the present study, along with the design, synthesis, and biological evaluation of a series of new spermine (Spm) analogues (1-23), a mixed structure-based (SB) and ligand-based (LB) protocol was applied. Binding modes of BSAO-PA modeled complexes led to clarify electrostatic and steric features likely affecting the BSAO-PA biochemical kinetics. LB and SB three-dimensional quantitative structure-activity relationship (Py-CoMFA and Py-ComBinE) models were developed by means of the 3d-qsar.com portal, and their analysis represents a strong basis for future design and synthesis of PA BSAO substrates for potential application in oxidative stress-induced chemotherapy.
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