6-Amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline: Insight into the Crystal Structure, Hirshfeld Surface Analysis and Computational Study

被引:18
作者
Babashkina, Maria G. [1 ]
Safin, Damir A. [1 ,2 ,3 ]
机构
[1] Kurgan State Univ, Adv Mat Ind & Biomed Lab, Sovetskaya Str 63-4, Kurgan 640020, Russia
[2] Ural Fed Univ, Innovat Ctr Chem & Pharmaceut Technol, Ekaterinburg, Russia
[3] Univ Tyumen, Tyumen, Russia
关键词
Quinoline; crystal structure; Hirshfeld surface analysis; computational study; DFT; MOLECULAR-ORBITAL METHODS;
D O I
10.1080/10406638.2022.2068622
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
In this work we report detailed structural and computational studies of 6-amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline (1). The structure is stabilized by the intramolecular N-H center dot center dot center dot N hydrogen bonds, C-H center dot center dot center dot F interactions, pi center dot center dot center dot pi interactions and C-F center dot center dot center dot F-C interactions. The listed interactions are also reflected on the Hirshfeld surfaces as well as the corresponding 2D fingerprint plots, which revealed that the crystal packing of 1 is mainly dictated by highly favored H center dot center dot center dot H and H center dot center dot center dot F contacts followed by also favored H center dot center dot center dot N, C center dot center dot center dot C and F center dot center dot center dot F contacts. The DFT calculations were performed to verify the structure of 1 as well as its electronic and optical properties. Compound 1 was predicted to exhibit preferred results for drug candidates in five parameters, namely lipophilicity, size, polarity, insolubility and flexibility. Furthermore, it was predicted that 1 is likely a potential inhibitor of family A G protein-coupled receptor and kinase; electrochemical transporter and voltage-gated ion channel; oxidoreductase, hydrolase, protease, family C G protein-coupled receptor and primary active transporter with the probabilities of 20.0%, 13.3% and 6.7%, respectively. At the same time, 1 was found to be active against Aryl hydrocarbon Receptor (AhR) and Mitochondrial Membrane Potential (MMP), hepatotoxic and mutagenic. According to the BOILED-Egg method for 1 the human blood-brain barrier (BBB) penetration property is negative and gastrointestinal absorption property is positive with the positive PGP effect on the molecule.
引用
收藏
页码:3324 / 3341
页数:18
相关论文
共 36 条
[1]   Molecular structure, spectroscopic studies and first-order molecular hyperpolarizabilities of p-amino acetanilide [J].
Abraham, Jose P. ;
Sajan, D. ;
Joe, I. Hubert ;
Jayakumar, V. S. .
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, 2008, 71 (02) :355-367
[2]   Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria [J].
Achan, Jane ;
Talisuna, Ambrose O. ;
Erhart, Annette ;
Yeka, Adoke ;
Tibenderana, James K. ;
Baliraine, Frederick N. ;
Rosenthal, Philip J. ;
D'Alessandro, Umberto .
MALARIA JOURNAL, 2011, 10
[3]   A review on anticancer potential of bioactive heterocycle quinoline [J].
Afzal, Obaid ;
Kumar, Suresh ;
Haider, Md Rafi ;
Ali, Md Rahmat ;
Kumar, Rajiv ;
Jaggi, Manu ;
Bawa, Sandhya .
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2015, 97 :871-910
[4]  
[Anonymous], 2016, GaussView
[5]   Antitumor effects of novel nickel-hydrazone complexes in lung cancer cells [J].
Ay, Burak ;
Sahin, Onur ;
Demir, Burcu Saygideger ;
Saygideger, Yasemin ;
Lopez-de-Luzuriaga, Jose M. ;
Mahmoudi, Ghodrat ;
Safin, Damir A. .
NEW JOURNAL OF CHEMISTRY, 2020, 44 (21) :9064-9072
[6]   Favipiravir: insight into the crystal structure, Hirshfeld surface analysis and computational study [J].
Babashkina, Maria G. ;
Frontera, Antonio ;
Kertman, Alexander, V ;
Saygideger, Yasemin ;
Murugavel, Swaminathan ;
Safin, Damir A. .
JOURNAL OF THE IRANIAN CHEMICAL SOCIETY, 2022, 19 (01) :85-94
[7]   ProTox-II: a webserver for the prediction of toxicity of chemicals [J].
Banerjee, Priyanka ;
Eckert, Andreas O. ;
Schrey, Anna K. ;
Preissner, Robert .
NUCLEIC ACIDS RESEARCH, 2018, 46 (W1) :W257-W263
[8]   DENSITY-FUNCTIONAL THERMOCHEMISTRY .3. THE ROLE OF EXACT EXCHANGE [J].
BECKE, AD .
JOURNAL OF CHEMICAL PHYSICS, 1993, 98 (07) :5648-5652
[9]   SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules [J].
Daina, Antoine ;
Michielin, Olivier ;
Zoete, Vincent .
SCIENTIFIC REPORTS, 2017, 7
[10]   A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules [J].
Daina, Antoine ;
Zoete, Vincent .
CHEMMEDCHEM, 2016, 11 (11) :1117-1121