51359-78-5Relevant articles and documents
Cationic N-confused porphyrin derivative as a better molecule scaffold for G-quadruplex recognition
Du, Yuhao,Zhang, Dan,Chen, Wei,Zhang, Ming,Zhou, Yangyang,Zhou, Xiang
, p. 1111 - 1116 (2010)
One N-confused porphyrin derivative was prepared and its first observation that it could stabilize G-quadruplex and possessed high selectivity over duplex DNA was made, furthermore, it was also proved to possess the capacity to induce a structural transition from the antiparallel to the mixed-type hybrid G-quadruplex structure.
A Chemoselective and Modular Post-Synthetic Multi-Functionalization of NHC-Platinum Complexes
Dahm, Georges,Borré, Etienne,Guichard, Gilles,Bellemin-Laponnaz, Stéphane
, p. 1665 - 1668 (2015)
We report oxime ligation in combination with metal ligand exchange as a novel orthogonal and practical approach to the multifunctionalization of NHC-platinum complexes. This strategy, which enables strong diversity enhancement of metallodrug candidates, could also be applied to selective bioconjugation. We report oxime ligation in combination with metal ligand exchange as a novel orthogonal and practical approach to the multi-functionalization of NHC-platinum complexes.
Discovery of novel CA-4 analogs as dual inhibitors of tubulin polymerization and PD-1/PD-L1 interaction for cancer treatment
Yang, Xuchao,Cheng, Binbin,Xiao, Yao,Xue, Mingming,Liu, Ting,Cao, Hao,Chen, Jianjun
, (2021)
A series of novel CA-4 analogs as dual inhibitors of tubulin polymerization and PD-1/PD-L1 were designed, synthesized and bio-evaluated. Among them, compound TP5 exhibited strongest inhibitory effects against five cancer cell lines with an IC50 value of 800 nM in HepG2 cells. In addition, mechanism studies revealed that TP5 could effectively inhibit tubulin polymerization, suppress HepG2 cells migration and colony formation, and cause cell arrest at G2/M phase and induce apoptosis. Furthermore, TP5 exhibited moderate anti-PD-1/PD-L1 activity with IC50 values of 48.76 μM in a homogenous time-resolved fluorescence (HTRF) assay. In vivo efficacy studies indicated that TP5 could significantly suppress tumor growth in an immune checkpoint humanized mouse model with a Tumor Growth Suppression (TGI) of 57.9% at 100 mg/kg without causing significant toxicity. Moreover, TP5 did not cause in vivo cardiotoxicity in BALB/c mice. These results suggest that the novel CA-4 analogs may serve as a starting point for developing more potent dual inhibitors of tubulin polymerization and PD-1/PD-L1.
Synthesis and evaluation of novel α-aminoamides containing an indole moiety for the treatment of neuropathic pain
Li, Haotian,Fan, Shiyong,Cheng, Jingchao,Zhang, Ping,Zhong, Bohua,Shi, Weiguo
, (2016)
The α-aminoamide family of sodium ion channel blockers have exhibited analgesic effects on neuropathic pain. Here, a series of novel α-aminoamides containing an indole ring were designed and synthesized. These compounds were evaluated in mice using a formalin test and they exhibited significant anti-allodynia activities. However, the analgesic mechanism of these compounds remains unclear; a subset of the synthesized compounds can only moderately inhibit the sodium ion channel, Nav1.7, in a whole-cell patch clamp assay. Overall, these results suggest that introduction of an indole moiety to α-aminoamide derivatives can significantly improve their bioactivity and further study is warranted.
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.
Self-reporting heavy atom-free photodynamic therapy agents
Demirok, Naime,Erbas-Cakmak, Sundus,Kayadibi Koygun, Gozde,Turkoglu, Gulsen,Yurt, Mediha Nur Zafer
, p. 9433 - 9437 (2020/12/15)
Two novel, self-reporting distyryl BODIPY-based photodynamic therapy agents functionalized with singlet oxygen responsive imidazole and tertiary amine moieties are developed. Heavy atom-free photosensitizers are demonstrated to have efficient photodynamic action in MCF7 cells. The fluorescence intensity of the photosensitizers is shown to be reduced as a result of 1O2 generation without any significant change in photodynamic activity. This journal is
