25015-92-3Relevant academic research and scientific papers
Design, synthesis and evaluation of novel 4-dimethylamine flavonoid derivatives as potential multi-functional anti-Alzheimer agents
Luo, Wen,Su, Ya-Bin,Hong, Chen,Tian, Run-Guo,Su, Lei-Peng,Wang, Yue-Qiao,Li, Yang,Yue, Jun-Jie,Wang, Chao-Jie
, p. 7275 - 7282 (2013)
A series of 4-dimethylamine flavonoid derivatives 5a-5r were designed, synthesized and evaluated as potential multi-functional anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity at the micromolar range (IC50, 1.83-33.20 μM for AChE and 0.82-11.45 μM for BChE). A Lineweaver-Burk plot indicated a mixed-type inhibition for compound 5j with AChE, and molecular modeling study showed that 5j targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, the derivatives showed potent self-induced Aβ aggregation inhibitory activity at 20 μM with percentage from 25% to 48%. In addition, some compounds (5j-5q) showed potent oxygen radical absorbance capacity (ORAC) ranging from 1.5- to 2.6-fold of the Trolox value. These compounds should be further investigated as multi-potent agents for the treatment of Alzheimer's disease.
Design, synthesis, biological evaluation, and molecular docking studies of some novel N,N-dimethylaminopropoxy-substituted aurones
Dalal, Sunita,Kumar, Gourav,Kumar, Ramesh,Kumar, Suresh,Kumari, Meena,Saroha, Bhavna
, (2021/10/25)
In continuation of our ongoing research on the discovery of novel and potentially bioactive aurones, we have designed and synthesized some novel N,N-dimethylaminopropoxy-substituted pyrazole-based aurones 10(a-l). These pyrazole-benzofuranone hybrid compounds were characterized by using their IR, 1H-NMR, 13C-NMR, and mass spectrometry data. Compound 10c was used as a model to further explicate the structure of tilted compounds by means of 1H-1H COSY, 1H-13C HMQC, 1H-13C HMBC, 1H-1H TOCSY, 1H-1H NOSEY, DEPT-45°, DEPT-90°, and DEPT-135° NMR spectra. The comparative molecular docking study of N,N-dimethylaminopropoxy-substituted pyrazole-based aurones and standard drugs (Ampicillin and Chloramphenicol) against Bacillus subtilis (PDB: 6tzp) active site was performed to determine the binding interactions, binding energy, and orientation of the molecules at the active site of the target protein. Out of these synthesized compounds, five best analogs (10b, 10f, 10h, 10k, and 10l) of docking results were also evaluated for their in vitro antibacterial potential against Bacillus subtilis to validate the docking results.
Design and biological evaluation of novel imidazolyl flavonoids as potent and selective protein tyrosine phosphatase inhibitors
Ge, Yu,Han, Rong Y.,Wang, Qing M.,Zhang, Ling
, p. 563 - 574 (2020/06/21)
Background: Protein tyrosine phosphatases 1B are considered to be a desirable vali-dated target for therapeutic development of type II diabetes and obesity. Methods: A new series of imidazolyl flavonoids as potential protein tyrosine phosphatase inhibi-to
Flavone inspired discovery of benzylidenebenzofuran-3(2H)-ones (aurones) as potent inhibitors of human protein kinase CK2
Bdzhola, V. G.,Bilokin, Y. V.,Borysenko, I. P.,Lukashov, S. S.,Protopopov, M. V.,Prykhod'ko, A. O.,Starosyla, S. A.,Vdovin, V. S.,Yarmoluk, S. M.
supporting information, (2020/07/21)
In this work, we describe the design, synthesis and SAR studies of 2-benzylidenebenzofuran-3-ones (aurones), a new family of potent inhibitors of CK2. A series of aurones have been synthesized. These compounds are structurally related to the synthetic flavones and showed nanomolar activities towards CK2. Biochemical tests revealed that 20 newly synthesized compounds inhibited CK2 with IC50 values in the nanomolar range. Further property-based optimization of aurones was performed, yielding a series of CK2 inhibitors with enhanced lipophilic efficiency. The most potent compound 12m (BFO13) has CLipE = 4.94 (CLogP = 3.5; IC50 = 3.6 nM) commensurable with the best known inhibitors of CK2.
Tryptophan compound, preparation method and application thereof
-
Paragraph 0030-0037; 0050-0052; 0058-0060, (2019/11/28)
The invention relates to a tryptophan compound, a preparation method and application thereof. The molecular formula is (Z)-(2-((2-(4-methoxybenzylidene)-3-oxo-2, 3-dihydrobenzofuran-6-yl)oxyl)acetyl)-D-tryptophan. The small molecule compound has a chiral center, and the absolute configuration is R configuration; the small molecule compound can reach a good inhibitory effect on thrombin, also has low toxicity, good druggability, and good medicinal potential, and provides a new potential option for clinical medication.
Identification of novel imidazole flavonoids as potent and selective inhibitors of protein tyrosine phosphatase
Zhang, Ling,Ge, Yu,Wang, Qing Ming,Zhou, Cheng-He
, (2019/04/17)
A series of imidazole flavonoids as new type of protein tyrosine phosphatase inhibitors were synthesized and characterized. Most of them gave potent protein phosphatase 1B (PTP1B) inhibitory activities. Especially, compound 11a could effectively inhibit P
A three-methoxy flavone salicylic acid derivatives and its anti-tumor activity (by machine translation)
-
Paragraph 0038-0039; 0040, (2019/05/08)
The invention discloses a three-methoxy flavone salicylic acid derivatives, can be used as a tumor blood vessel and tumor cell glycolysis double-target inhibitors, in order to block the tumor tissue has generated the blood vessel, in order to block tumor cell nutrient supply, at the same time inhibiting glycolysis process of tumor cells, tumor cells in the absence of nutrition, also cannot use their own glycolysis proliferate, thereby accelerating the death of tumor cells. The design of this invention is of tumor blood vessel with the glycolysis double-target inhibitor has the role of both, but than the combined medication safer and more convenient. (by machine translation)
Design, synthesis, and preliminary biological evaluation of 3′,4′,5′-trimethoxy flavonoid salicylate derivatives as potential anti-tumor agents
Deng, Xiangping,Liu, Renbo,Li, Junjian,Li, Zhongli,Liu, Juan,Xiong, Runde,Lei, Xiaoyong,Zheng, Xing,Xie, Zhizhong,Tang, Guotao
, p. 1874 - 1884 (2019/01/28)
According to the pharmacophore combination principle, a set of new 3′,4′,5′-trimethoxy flavonoid salicylate derivatives were designed, synthesized, and evaluated for biological activity. The cytotoxicity evaluation revealed that compound 10v exhibited higher potency than 5-Fu against HCT-116 cells. Preliminary biological activity studies showed that compound 10v could inhibit the colony formation and migration of HCT-116 cells. Besides, the Hoechst 33258 staining assay and flow cytometry revealed that treatment with compound 10v induced the apoptosis of HCT-116 cells in a concentration-dependent manner, while it had no effect on their cell cycle. The WB analysis suggested that HIF-1α, tubulin, HK-2, and PFK might be the potential pharmacophore targets of compound 10v. Tubulin was a potential drug target for compound 10v, which was explained by analyzing the crystal structure of compound 10v complexed with tubulin. These results indicated that compound 10v might be a promising anti-tumor agent candidate, deserving further optimization and evaluation.
Synthesis of novel pyrazole derivatives and their tumor cell growth inhibitory activity
Cui, Ying-Jie,Tang, Long-Qian,Zhang, Cheng-Mei,Liu, Zhao-Peng
, (2019/01/23)
To find novel antitumor agents, a series of 1H-benzofuro[3,2-c]pyrazole derivatives 4a-e were designed and synthesized. The treatment of 6-methoxybenzofuran-3(2H)-one 3 with LiHMDS in anhydrous tetrahydrofuran (THF) followed by reaction with 3-substitued phenyl isothiocyanate gave the thioamide intermediates, which underwent condensation with hydrazine monohydrate in dioxane/EtOH (1:1) to provide the benzofuropyrazole derivatives 4a–e as well as the unexpected pyrazole derivatives 5a–e. In tumor cell growth inhibitory assay, all the benzofuropyrazole derivatives were not active against the breast tumor MCF-7 cell, only 4a was highly active and more potent than ABT-751 against the leukemia K562 (GI50 = 0.26 μM) and lung tumor A549 cells (GI50 = 0.19 μM), while other benzofuropyrazoles showed very weak inhibitory activity. In contrast, the pyrazoles 5a-e were in general more potent than the benzofuropyrazoles 4a–e. Compound 5a exhibited a similar tendency to that of 4a with high potency against K562 and A549 cells but weak effects on MCF-7 cell. Both pyrazoles 5b and 5e exhibited high inhibitory activities against K562, MCF-7 and A549 cells. The most active compound 5b was much more potent than ABT-751 against K562 and A549 cells with GI50 values of 0.021 and 0.69 M, respectively. Moreover, 5b was identified as a novel tubulin polymerization inhibitor with an IC50 of 7.30 M.
Drug design, synthesis and in vitro evaluation of substituted benzofurans as hsp90 inhibitors
Kadasi, Sundeep,Costa, Thadeu E.M.M.,Arukala, Neha,Toshakani, Mallika,Duggineti, Chaitanya,Thota, Sreekanth,Gupta, Sayan D.,Raj, Shiva,Penido, Carmen,Henriques, Maria G.,Raghavendra, Nulgumnalli M.
, p. 44 - 52 (2018/02/14)
Background: Heat shock protein 90 is a molecular chaperone required for the stability and function of several client proteins that promote cancer cell growth and/or survival. Discovery of Hsp90 inhibitors has emerged as an attractive target of research in cancer therapeutics. Natural products like geldanamycin and radicicol are established Hsp90 inhibitors, but face limitations with toxicity and inactivity, by in vivo studies respectively. However, they lay the logical starting point for the design of novel synthetic or semi-synthetic congeners as Hsp90 inhibitors. Objective: In this article, the structure based drug design of substituted 2-aryl/heteroarylidene-6- hydroxybenzofuran-3(2H)-one analogues to optimize and mimic the pharmacophoric interactions of the valid Hsp90 inhibitor radicicolis focused. Method: In silico docking study was performed by Surflex dock-Geom (SYBYL- X 1.2 drug discovery suite) and the designed ligands were chemically synthesized by conventional method using resorcinol and chlororesorcinol as starting materials. Two dimensional chemical similarity search was carried out to identify the chemical space of 'SY' series in comparison with reported Hsp90 inhibitors. The in vitro cell proliferation assay (resazurin reduction method) and proteomic investigation (DARTS) was carried out on whole cell lysate to evaluate anticancer activity. Results: The chemical structures of all the synthesized compounds were confirmed by IR, 1H-NMR and Mass spectral analysis. The results of chemical similarity search show that SY series fit it in the chemical space defined by existing Hsp90 inhibitors. In vitro cell proliferation assay, against human melanoma and breast cancer cell lines, identified 'SY3' as the promising anticancer agent amongst the series. Conclusion: Docking studies, 2D chemical similarity search, resazurin reduction assay and qualitative proteomic analysis identify 'SY3'as a promising Hsp90 inhibitor amongst the series.
