65737-59-9Relevant academic research and scientific papers
Novel quinolone-based potent and selective HDAC6 inhibitors: Synthesis, molecular modeling studies and biological investigation
Relitti, Nicola,Saraswati, A. Prasanth,Chemi, Giulia,Brindisi, Margherita,Brogi, Simone,Herp, Daniel,Schmidtkunz, Karin,Saccoccia, Fulvio,Ruberti, Giovina,Ulivieri, Cristina,Vanni, Francesca,Sarno, Federica,Altucci, Lucia,Lamponi, Stefania,Jung, Manfred,Gemma, Sandra,Butini, Stefania,Campiani, Giuseppe
, (2020/11/24)
In this work we describe the synthesis of potent and selective quinolone-based histone deacetylase 6 (HDAC6) inhibitors. The quinolone moiety has been exploited as an innovative bioactive cap-group for HDAC6 inhibition; its synthesis was achieved by applying a multicomponent reaction. The optimization of potency and selectivity of these products was performed by employing computational studies which led to the discovery of the diethylaminomethyl derivatives 7g and 7k as the most promising hit molecules. These compounds were investigated in cellular studies to evaluate their anticancer effect against colon (HCT-116) and histiocytic lymphoma (U9347) cancer cells, showing good to excellent potency, leading to tumor cell death by apoptosis induction. The small molecules 7a, 7g and 7k were able to strongly inhibit the cytoplasmic and slightly the nuclear HDAC enzymes, increasing the acetylation of tubulin and of the lysine 9 and 14 of histone 3, respectively. Compound 7g was also able to increase Hsp90 acetylation levels in HCT-116 cells, thus further supporting its HDAC6 inhibitory profile. Cytotoxicity and mutagenicity assays of these molecules showed a safe profile; moreover, the HPLC analysis of compound 7k revealed good solubility and stability profile.
Spin-Center Shift-Enabled Direct Enantioselective α-Benzylation of Aldehydes with Alcohols
Nacsa, Eric D.,MacMillan, David W. C.
supporting information, p. 3322 - 3330 (2018/03/13)
Nature routinely engages alcohols as leaving groups, as DNA biosynthesis relies on the removal of water from ribonucleoside diphosphates by a radical-mediated "spin-center shift" (SCS) mechanism. Alcohols, however, remain underused as alkylating agents in synthetic chemistry due to their low reactivity in two-electron pathways. We report herein an enantioselective α-benzylation of aldehydes using alcohols as alkylating agents based on the mechanistic principle of spin-center shift. This strategy harnesses the dual activation modes of photoredox and organocatalysis, engaging the alcohol by SCS and capturing the resulting benzylic radical with a catalytically generated enamine. Mechanistic studies provide evidence for SCS as a key elementary step, identify the origins of competing reactions, and enable improvements in chemoselectivity by rational photocatalyst design.
Semiconductor quantum dots photosensitizing release of anticancer drug
Liu, Zhenzhen,Lin, Qiuning,Huang, Qi,Liu, Hui,Bao, Chunyan,Zhang, Wenjin,Zhong, Xinhua,Zhu, Linyong
supporting information; experimental part, p. 1482 - 1484 (2011/03/20)
A new photo-controlled anticancer drug release system is reported based on the photo-induced electron transfer (PET) between semiconductor quantum dots (QDs) and N-methyl-4-picolinium (NAP) ester 1 under the excitation of visible light.
