QUINOLINE

General Information

Mainterm	QUINOLINE
Doc Type	NIL
CAS Reg.No.(or other ID)	91-22-5
Regnum

From www.fda.gov

Computed Descriptors

Download SDF

2D Structure
CID	7047
IUPAC Name	quinoline
InChI	InChI=1S/C9H7N/c1-2-6-9-8(4-1)5-3-7-10-9/h1-7H
InChI Key	SMWDFEZZVXVKRB-UHFFFAOYSA-N
Canonical SMILES	C1=CC=C2C(=C1)C=CC=N2
Molecular Formula	C9H7N
Wikipedia	quinoline

From Pubchem

Computed Properties

Property Name	Property Value
Molecular Weight	129.162
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	1
Rotatable Bond Count	0
Complexity	111.0
CACTVS Substructure Key Fingerprint	A A A D c Y B y A A A A A A A A A A A A A A A A A A A A A A A A A A A 8 Q A A A A A A A A A C x 8 A A A H A A A A A A A D A j B H g Q 8 w P I I E A C g A z R n R A C C g C A x A i A I 2 C A 4 Z J g I I O L A k Z G E I A h g g A D I y A c Q g I A O A A A A A A A C A A A A A A A A A A Q A A A A A A A A A A A = =
Topological Polar Surface Area	12.9
Monoisotopic Mass	129.058
Exact Mass	129.058
Compound Is Canonicalized	True
Formal Charge	0
Heavy Atom Count	10
Defined Atom Stereocenter Count	0
Undefined Atom Stereocenter Count	0
Defined Bond Stereocenter Count	0
Undefined Bond Stereocenter Count	0
Isotope Atom Count	0
Covalently-Bonded Unit Count	1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model	Result	Probability
Absorption
Blood-Brain Barrier	BBB+	0.9866
Human Intestinal Absorption	HIA+	0.9961
Caco-2 Permeability	Caco2+	0.7659
P-glycoprotein Substrate	Non-substrate	0.7617
P-glycoprotein Inhibitor	Non-inhibitor	0.9517
P-glycoprotein Inhibitor	Non-inhibitor	0.9754
Renal Organic Cation Transporter	Non-inhibitor	0.7613
Distribution
Subcellular localization	Lysosome	0.6206
Metabolism
CYP450 2C9 Substrate	Non-substrate	0.8313
CYP450 2D6 Substrate	Non-substrate	0.8351
CYP450 3A4 Substrate	Non-substrate	0.7555
CYP450 1A2 Inhibitor	Inhibitor	0.9188
CYP450 2C9 Inhibitor	Inhibitor	0.5260
CYP450 2D6 Inhibitor	Non-inhibitor	0.5667
CYP450 2C19 Inhibitor	Inhibitor	0.8774
CYP450 3A4 Inhibitor	Non-inhibitor	0.8837
CYP Inhibitory Promiscuity	Low CYP Inhibitory Promiscuity	0.6283
Excretion
Toxicity
Human Ether-a-go-go-Related Gene Inhibition	Weak inhibitor	0.9575
Human Ether-a-go-go-Related Gene Inhibition	Non-inhibitor	0.8709
AMES Toxicity	AMES toxic	0.9107
Carcinogens	Non-carcinogens	0.9312
Fish Toxicity	High FHMT	0.5681
Tetrahymena Pyriformis Toxicity	High TPT	0.8189
Honey Bee Toxicity	High HBT	0.5608
Biodegradation	Not ready biodegradable	0.8030
Acute Oral Toxicity	III	0.6050
Carcinogenicity (Three-class)	Non-required	0.6901

From admetSAR

ADMET Predicted Profile --- Regression

Model	Value	Unit
Absorption
Aqueous solubility	-2.8427	LogS
Caco-2 Permeability	1.7335	LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity	2.2813	LD50, mol/kg
Fish Toxicity	1.7656	pLC50, mg/L
Tetrahymena Pyriformis Toxicity	0.2758	pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of Exposure	Oral ; inhalation
Mechanism of Toxicity	The ability of PAH's to bind to blood proteins such as albumin allows them to be transported throughout the body. Many PAH's induce the expression of cytochrome P450 enzymes, especially CYP1A1, CYP1A2, and CYP1B1, by binding to the aryl hydrocarbon receptor or glycine N-methyltransferase protein. These enzymes metabolize PAH's into their toxic intermediates. The reactive metabolites of PAHs (epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations) covalently bind to DNA and other cellular macromolecules, initiating mutagenesis and carcinogenesis.
Metabolism	PAH metabolism occurs in all tissues, usually by cytochrome P-450 and its associated enzymes. PAHs are metabolized into reactive intermediates, which include epoxide intermediates, dihydrodiols, phenols, quinones, and their various combinations. The phenols, quinones, and dihydrodiols can all be conjugated to glucuronides and sulfate esters; the quinones also form glutathione conjugates.
Toxicity Values	LD50: 331 mg/kg (Oral, Rat) LD50: 540 mg/kg (Dermal, Rabbit)
Lethal Dose	None
Carcinogenicity (IARC Classification)	Not listed by IARC. IARC has evaluated related PAHs .
Minimum Risk Level	None
Health Effects	PAHs are carcinogens and have been associated with the increased risk of skin, respiratory tract, bladder, stomach, and kidney cancers. They may also cause reproductive effects and depress the immune system. (L10)
Treatment	There is no know antidote for PAHs. Exposure is usually handled with symptomatic treatment.
Reference	Santodonato J, Howard P, Basu D: Health and ecological assessment of polynuclear aromatic hydrocarbons. J Environ Pathol Toxicol. 1981 Sep;5(1):1-364.[7310260 ] Uno S, Dragin N, Miller ML, Dalton TP, Gonzalez FJ, Nebert DW: Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract. Free Radic Biol Med. 2008 Feb 15;44(4):570-83. Epub 2007 Nov 12.[17997381 ] Padros J, Pelletier E: In vivo formation of (+)-anti-benzo[a]pyrene diol-epoxide-plasma albumin adducts in fish. Mar Environ Res. 2000 Jul-Dec;50(1-5):347-51.[11460716 ] Ruger A, Schwarz G, Lingens F: Microbial metabolism of quinoline and related compounds. XIX. Degradation of 4-methylquinoline and quinoline by Pseudomonas putida K1. Biol Chem Hoppe Seyler. 1993 Jul;374(7):479-88.[8216899 ] Van Caekenberghe DL, Pattyn SR: In vitro activity of ciprofloxacin compared with those of other new fluorinated piperazinyl-substituted quinoline derivatives. Antimicrob Agents Chemother. 1984 Apr;25(4):518-21.[6732221 ] Xu XD, Hu XR, Yang JS: [Review of studies on active components of antitumor medicinal plants]. Zhongguo Zhong Yao Za Zhi. 2008 Sep;33(17):2073-81.[19066044 ] Musiol R, Serda M, Hensel-Bielowka S, Polanski J: Quinoline-based antifungals. Curr Med Chem. 2010;17(18):1960-73.[20377510 ] Solomon VR, Lee H: Quinoline as a privileged scaffold in cancer drug discovery. Curr Med Chem. 2011;18(10):1488-508.[21428893 ]

From T3DB

Taxonomic Classification

Kingdom	Organic compounds
Superclass	Organoheterocyclic compounds
Class	Quinolines and derivatives
Subclass	Not available
Intermediate Tree Nodes	Not available
Direct Parent	Quinolines and derivatives
Alternative Parents	Organopnictogen compounds Azacyclic compounds Hydrocarbon derivatives Benzenoids Heteroaromatic compounds Organonitrogen compounds
Molecular Framework	Aromatic heteropolycyclic compounds
Substituents	Quinoline - Benzenoid - Pyridine - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Organopnictogen compound - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteropolycyclic compound
Description	This compound belongs to the class of organic compounds known as quinolines and derivatives. These are compounds containing a quinoline moiety, which consists of a benzene ring fused to a pyrimidine ring to form benzo[b]azabenzene.

From ClassyFire

Targets

Target Details

Proteinase-activated receptor 1

General Function:: Thrombin receptor activity
Specific Function:: High affinity receptor for activated thrombin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation and in vascular development.
Gene Name:: F2R
Uniprot ID:: P25116
Molecular Weight:: 47439.83 Da

References

Clasby MC, Chackalamannil S, Czarniecki M, Doller D, Eagen K, Greenlee WJ, Lin Y, Tsai H, Xia Y, Ahn HS, Agans-Fantuzzi J, Boykow G, Chintala M, Foster C, Bryant M, Lau J: Discovery and synthesis of a novel series of quinoline-based thrombin receptor (PAR-1) antagonists. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1544-8. Epub 2005 Dec 27. [16380251 ]

Target Details

Aryl hydrocarbon receptor

General Function:: Transcription regulatory region dna binding
Specific Function:: Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.
Gene Name:: AHR
Uniprot ID:: P35869
Molecular Weight:: 96146.705 Da

References

Wikipedia. Benzopyrene. Last Updated 22 January 2009. : http://en.wikipedia.org/wiki/Benzopyrene [11460716 ]

Target Details

Glycine N-methyltransferase

General Function:: Glycine n-methyltransferase activity
Specific Function:: Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Gene Name:: GNMT
Uniprot ID:: Q14749
Molecular Weight:: 32742.0 Da

References

Wikipedia. Benzopyrene. Last Updated 22 January 2009. : http://en.wikipedia.org/wiki/Benzopyrene [11460716 ]

Target Details

Cytochrome P450 2D6

General Function:: Steroid hydroxylase activity
Specific Function:: Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:: CYP2D6
Uniprot ID:: P10635
Molecular Weight:: 55768.94 Da

References

Strobl GR, von Kruedener S, Stockigt J, Guengerich FP, Wolff T: Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies. J Med Chem. 1993 Apr 30;36(9):1136-45. [8487254 ]

Target Details

Nuclear receptor ROR-beta

General Function:: Zinc ion binding
Specific Function:: Nuclear receptor that binds DNA as a monomer to ROR response elements (RORE) containing a single core motif half-site 5'-AGGTCA-3' preceded by a short A-T-rich sequence. Considered to have intrinsic transcriptional activity, have some natural ligands such as all-trans retinoic acid (ATRA) and other retinoids which act as inverse agonists repressing the transcriptional activity. Required for normal postnatal development of rod and cone photoreceptor cells. Modulates rod photoreceptors differentiation at least by inducing the transcription factor NRL-mediated pathway. In cone photoreceptor cells, regulates transcription of OPN1SW. Involved in the regulation of the period length and stability of the circadian rhythm. May control cytoarchitectural patterning of neocortical neurons during development. May act in a dose-dependent manner to regulate barrel formation upon innervation of layer IV neurons by thalamocortical axons. May play a role in the suppression of osteoblastic differentiation through the inhibition of RUNX2 transcriptional activity (By similarity).Isoform 1 is critical for hindlimb motor control and for the differentiation of amacrine and horizontal cells in the retina. Regulates the expression of PTF1A synergistically with FOXN4 (By similarity).
Gene Name:: RORB
Uniprot ID:: Q92753
Molecular Weight:: 53219.385 Da

References

Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]

From T3DB