Biological evaluation of quinoline derivatives as inhibitors of human dihydroorotate dehydrogenase

MedChemComm ◽  
2016 ◽  
Vol 7 (5) ◽  
pp. 853-858 ◽  
Author(s):  
Jiawei Wang ◽  
Yanyan Diao ◽  
Junsheng Zhu ◽  
Shiliang Li ◽  
Zhenjiang Zhao ◽  
...  
Keyword(s):  
Biological Evaluation ◽  
Quinoline Derivatives ◽  
Dihydroorotate Dehydrogenase ◽  
X Ray ◽  
X Ray Crystallography

Compound A9 was identified as an inhibitor against hDHODH and its interactions were verified by TSA, SPR and X-ray crystallography.

Direct Synthesis of 6H-Chromeno[3,4-b]quinolin-6-ol Derivatives from Substituted 3-Nitro-2H-chromenes and 2-Nitrobenzaldehydes Mediated by Fe/AcOH System

Synthesis ◽  
2017 ◽  
Vol 50 (06) ◽  
pp. 1350-1358 ◽  
Author(s):  
Cunde Wang ◽  
Xushun Qing ◽  
Ting Wang ◽  
Chenlu Dai ◽  
Zhenjie Su
Keyword(s):  
Acetic Acid ◽  
Nucleophilic Addition ◽  
Aldol Condensation ◽  
Direct Synthesis ◽  
Reductive Cyclization ◽  
Quinoline Derivatives ◽  
Acid System ◽  
X Ray ◽  
X Ray Crystallography ◽  
Sequential Reduction

An efficient iron/acetic acid system-mediated reductive cyclization reaction of substituted 2-aryl-3-nitro-2H-chromenes with substituted 2-nitrobenzaldehydes for the synthesis of 6-aryl-6H-chromeno[3,4-b]quinolines was developed. This reaction involves the sequential reduction, hydrolysis, aldol condensation, intramolecular addition, and the nucleophilic addition of substituted 2-aryl-3-nitro-2H-chromenes with substituted 2-nitrobenzaldehydes to give the corresponding 6H-chromeno[3,4-b]quinolines. This transformation provides a straightforward synthetic protocol for constructing substituted 6H-chromeno[3,4-b]quinoline derivatives. The structures of three typical products were confirmed by X-ray crystallography.

Asymmetric total synthesis, x-ray crystallography, and preliminary biological evaluation of 1-(1'-hydroxyethyl)-25-hydroxyvitamin D3 analogs of natural calcitriol

1993 ◽  
Vol 58 (25) ◽  
pp. 7209-7215 ◽  
Author(s):  
Gary H. Posner ◽  
Haiyan Dai ◽  
Kamyar Afarinkia ◽  
N. Narasimha Murthy ◽  
Kate Z. Guyton ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Biological Evaluation ◽  
Asymmetric Total Synthesis ◽  
X Ray ◽  
X Ray Crystallography

Structure-Based Design: Synthesis, X-ray Crystallography, and Biological Evaluation of N-Substituted-4-Hydroxy-2-Quinolone-3-Carboxamides as Potential Cytotoxic Agents

2018 ◽  
Vol 18 (2) ◽  
pp. 263-276 ◽  
Author(s):  
Dima A. Sabbah ◽  
Bayan Hishmah ◽  
Kamal Sweidan ◽  
Sanaa Bardaweel ◽  
Murad AlDamen ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Caspase 3 ◽  
Human Colon ◽  
Docking Studies ◽  
Biological Evaluation ◽  
X Ray ◽  
X Ray Crystallography ◽  
Human Colon Carcinoma ◽  
Glide Docking ◽  
Hct 116

Background: Oncogenic potential of phosphatidylinositol 3-kinase (PI3Kα) has been highlighted as a therapeutic target for anticancer drug design. Objective: Target compounds were designed to address the effect of different substitution patterns at the N atom of the carboxamide moiety on the bioactivity of this series. Methods: Synthesis of the targeted compounds, crystallography, biological evaluation tests against human colon carcinoma (HCT-116), and Glide docking studies. Results: A new series of N-substituted- 4-hydroxy-2-quinolone-3-carboxamides was prepared and characterized by means of FT-IR, 1H and 13C NMR, and elemental analysis. In addition, the identity of the core nucleus 5 was successfully characterized with the aid of X-ray crystallography. Biological activity of prepared compounds was investigated in vitro against human colon carcinoma (HCT-116) cell line. Results revealed that these compounds inhibit cell proliferation and induce apoptosis through an increase in caspase-3 activity and a decrease in DNA cellular content. Compounds 7, 14, and 17 which have H-bond acceptor moiety on p-position displayed promising PI3Kα inhibitory activity. On the other hand, derivatives tailored with bulky and hydrophobic motifs (16 and 18) on o- and m-positions exhibited moderate activity. Molecular docking studies against PI3Kα and caspase-3 showed an agreement between the predicted binding affinity (ΔGobsd) and IC50 values of the derivatives for the caspase-3 model. Furthermore, Glide docking studies against PI3Kα demonstrated that the newly synthesized compounds accommodate PI3Kα kinase catalytic domain and form H-bonding with key binding residues. Conclusion: The series exhibited a potential PI3Kα inhibitory activity in HCT-116 cell line.

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