ID: ALA55934

Max Phase: Preclinical

Molecular Formula: C10H6O2

Molecular Weight: 158.16

Molecule Type: Small molecule

Representations

Synonyms (4): 1,4-Naphtho-Quinone | 1,4-Naphthoquinone | Naphthalene-1,4-Dione | Naphthoquinone 1
Synonyms from Alternative Forms(4):

Canonical SMILES:  O=C1C=CC(=O)c2ccccc21

Standard InChI:  InChI=1S/C10H6O2/c11-9-5-6-10(12)8-4-2-1-3-7(8)9/h1-6H

Standard InChI Key:  FRASJONUBLZVQX-UHFFFAOYSA-N

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 158.16

Molecular Weight (Monoisotopic): 158.0368

AlogP: 1.62

#Rotatable Bonds: 0

Polar Surface Area: 34.14

Molecular Species: NEUTRAL

HBA: 2

HBD: 0

#RO5 Violations: 0

HBA (Lipinski): 2

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa:

CX LogP: 1.49

CX LogD: 1.49

Aromatic Rings: 1

Heavy Atoms: 12

QED Weighted: 0.57

Np Likeness Score: 0.49

References

1. Gordaliza M, Miguel del Corral J, Angeles Castro M, Mar Mahiques M, Garcia-Gravalos M, San Feliciano A.  (1996)  Synthesis and bioactivity of new antineoplastic terpenylquinones,  6  (15): [10.1016/0960-894X(96)00326-5]

2. Ryu CK, Jung SH, Lee JA, Kim HJ, Lee SH, Chung JH..  (1999)  6-arylamino-5,8-quinolinediones and 7-arylamino-5,8-isoquinolinediones as inhibitors of endothelium-dependent vasorelaxation.,  9  (17): [PMID:10498190] [10.1016/s0960-894x(99)00411-4]

3. Singh SB, Graham PL, Reamer RA, Cordingley MG..  (2001)  Discovery, total synthesis, HRV 3C-protease inhibitory activity, and structure-activity relationships of 2-methoxystypandrone and its analogues.,  11  (24): [PMID:11720861] [10.1016/s0960-894x(01)00648-5]

4. Plyta ZF, Li T, Papageorgiou VP, Mellidis AS, Assimopoulou AN, Pitsinos EN, Couladouros EA..  (1998)  Inhibition of topoisomerase I by naphthoquinone derivatives.,  8  (23): [PMID:9873739] [10.1016/s0960-894x(98)00600-3]

5. Hodnett EM, Wongwiechintana C, Dunn WJ, Marrs P..  (1983)  Substituted 1,4-naphthoquinones vs. the ascitic sarcoma 180 of mice.,  26  (4): [PMID:6834390] [10.1021/jm00358a021]

6. Moret EE, de Boer M, Hilbers HW, Tollenaere JP, Janssen LH, Holthuis JJ, Driebergen RJ, Verboom W, Reinhoudt DN..  (1996)  In vivo activity and hydrophobicity of cytostatic aziridinyl quinones.,  39  (3): [PMID:8576915] [10.1021/jm9405147]

7. Krajewska B, Zaborska W..  (2007)  Double mode of inhibition-inducing interactions of 1,4-naphthoquinone with urease: arylation versus oxidation of enzyme thiols.,  15  (12): [PMID:17416528] [10.1016/j.bmc.2007.03.071]

8. Mahapatra A, Mativandlela SP, Binneman B, Fourie PB, Hamilton CJ, Meyer JJ, van der Kooy F, Houghton P, Lall N..  (2007)  Activity of 7-methyljuglone derivatives against Mycobacterium tuberculosis and as subversive substrates for mycothiol disulfide reductase.,  15  (24): [PMID:17888665] [10.1016/j.bmc.2007.08.064]

9. Valente C, Moreira R, Guedes RC, Iley J, Jaffar M, Douglas KT..  (2007)  The 1,4-naphthoquinone scaffold in the design of cysteine protease inhibitors.,  15  (15): [PMID:17532221] [10.1016/j.bmc.2007.04.068]

10. Fedorov O, Marsden B, Pogacic V, Rellos P, Müller S, Bullock AN, Schwaller J, Sundström M, Knapp S..  (2007)  A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.,  104  (51): [PMID:18077363] [10.1073/pnas.0708800104]

11. Kumar S, Malachowski WP, DuHadaway JB, LaLonde JM, Carroll PJ, Jaller D, Metz R, Prendergast GC, Muller AJ..  (2008)  Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors.,  51  (6): [PMID:18318466] [10.1021/jm7014155]

12. Konoshima T, Kozuka M, Koyama J, Okatani T, Tagahara K, Tokuda H..  (1989)  Studies on inhibitors of skin tumor promotion, VI. Inhibitory effects of quinones on Epstein-Barr virus activation.,  52  (5): [PMID:2558164] [10.1021/np50065a012]

13. Cao S, Murphy BT, Foster C, Lazo JS, Kingston DG..  (2009)  Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases.,  17  (6): [PMID:19028102] [10.1016/j.bmc.2008.10.090]

14. John S, Thangapandian S, Sakkiah S, Lee KW..  (2010)  Identification of potent virtual leads to design novel indoleamine 2,3-dioxygenase inhibitors: pharmacophore modeling and molecular docking studies.,  45  (9): [PMID:20580138] [10.1016/j.ejmech.2010.05.057]

15. Kokel D, Li Y, Qin J, Xue D..  (2006)  The nongenotoxic carcinogens naphthalene and para-dichlorobenzene suppress apoptosis in Caenorhabditis elegans.,  2  (6): [PMID:16699520] [10.1038/nchembio791]

16. PubChem BioAssay data set, 

17. Coelho Cerqueira E, Netz PA, Diniz C, Petry do Canto V, Follmer C..  (2011)  Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO.,  19  (24): [PMID:22071524] [10.1016/j.bmc.2011.10.049]

18. Shukla S, Srivastava RS, Shrivastava SK, Sodhi A, Kumar P.  (2013)  Synthesis, characterization, in vitro anticancer activity, and docking of Schiff bases of 4-amino-1,2-naphthoquinone,  22  (4): [10.1007/s00044-012-0150-7]

19. Josey BJ, Inks ES, Wen X, Chou CJ..  (2013)  Structure-activity relationship study of vitamin k derivatives yields highly potent neuroprotective agents.,  56  (3): [PMID:23327468] [10.1021/jm301485d]

20. Bhasin D, Chettiar SN, Etter JP, Mok M, Li PK..  (2013)  Anticancer activity and SAR studies of substituted 1,4-naphthoquinones.,  21  (15): [PMID:23791367] [10.1016/j.bmc.2013.05.017]

21. Korwar S, Nguyen T, Ellis KC..  (2014)  Preparation and evaluation of deconstruction analogues of 7-deoxykalafungin as AKT kinase inhibitors.,  24  (1): [PMID:24321345] [10.1016/j.bmcl.2013.11.020]

22. Bremer PT, Hixon MS, Janda KD..  (2014)  Benzoquinones as inhibitors of botulinum neurotoxin serotype A.,  22  (15): [PMID:24984937] [10.1016/j.bmc.2014.06.004]

23. Yao BL, Mai YW, Chen SB, Xie HT, Yao PF, Ou TM, Tan JH, Wang HG, Li D, Huang SL, Gu LQ, Huang ZS..  (2015)  Design, synthesis and biological evaluation of novel 7-alkylamino substituted benzo[a]phenazin derivatives as dual topoisomerase I/II inhibitors.,  92  [PMID:25599951] [10.1016/j.ejmech.2015.01.024]

24. PubChem BioAssay data set, 

25. Huber-Villaume S, Revelant G, Sibille E, Philippot S, Morabito A, Dunand S, Chaimbault P, Bagrel D, Kirsch G, Hesse S, Schohn H..  (2016)  2-(Thienothiazolylimino)-1,3-thiazolidin-4-ones inhibit cell division cycle 25 A phosphatase.,  24  (13): [PMID:27178385] [10.1016/j.bmc.2016.04.063]

26. Janeczko M, Demchuk OM, Strzelecka D, Kubiński K, Masłyk M..  (2016)  New family of antimicrobial agents derived from 1,4-naphthoquinone.,  124  [PMID:27783973] [10.1016/j.ejmech.2016.10.034]

27. Ravez S, Corbet C, Spillier Q, Dutu A, Robin AD, Mullarky E, Cantley LC, Feron O, Frédérick R..  (2017)  α-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH).,  60  (4): [PMID:28085281] [10.1021/acs.jmedchem.6b01166]

28. Tomek P, Palmer BD, Flanagan JU, Sun C, Raven EL, Ching LM..  (2017)  Discovery and evaluation of inhibitors to the immunosuppressive enzyme indoleamine 2,3-dioxygenase 1 (IDO1): Probing the active site-inhibitor interactions.,  126  [PMID:28011425] [10.1016/j.ejmech.2016.12.029]

29. Lenstra DC, Al Temimi AHK, Mecinović J..  (2018)  Inhibition of histone lysine methyltransferases G9a and GLP by ejection of structural Zn(II).,  28  (7): [PMID:29519735] [10.1016/j.bmcl.2018.02.043]

30. Dallaston MA, Rajan S, Chekaiban J, Wibowo M, Cross M, Coster MJ, Davis RA, Hofmann A..  (2017)  Dichloro-naphthoquinone as a non-classical inhibitor of the mycobacterial carbonic anhydrase Rv3588c.,  8  (6): [PMID:30108843] [10.1039/C7MD00090A]

31. Huang R, Jing X, Huang X, Pan Y, Fang Y, Liang G, Liao Z, Wang H, Chen Z, Zhang Y..  (2020)  Bifunctional Naphthoquinone Aromatic Amide-Oxime Derivatives Exert Combined Immunotherapeutic and Antitumor Effects through Simultaneous Targeting of Indoleamine-2,3-dioxygenase and Signal Transducer and Activator of Transcription 3.,  63  (4): [PMID:31999451] [10.1021/acs.jmedchem.9b01386]

32. Stevens M, Abdeen S, Salim N, Ray AM, Washburn A, Chitre S, Sivinski J, Park Y, Hoang QQ, Chapman E, Johnson SM..  (2019)  HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules.,  29  (9): [PMID:30852084] [10.1016/j.bmcl.2019.02.028]

33. Intagliata S, Salerno L, Ciaffaglione V, Leonardi C, Fallica AN, Carota G, Amata E, Marrazzo A, Pittalà V, Romeo G..  (2019)  Heme Oxygenase-2 (HO-2) as a therapeutic target: Activators and inhibitors.,  183  [PMID:31550661] [10.1016/j.ejmech.2019.111703]

34. Ellen Van Damme.  (2021)  Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity,  [10.6019/CHEMBL4651402]

35. Du L,Wang X,Cui G,Xu B.  (2021)  Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors.,  29  [PMID:33246256] [10.1016/j.bmc.2020.115878]

36. Oliveri V.  (2019)  Toward the discovery and development of effective modulators of α-synuclein amyloid aggregation.,  167  [PMID:30743095] [10.1016/j.ejmech.2019.01.045]

37. Cui J, Jia J..  (2021)  Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors.,  225  [PMID:34438124] [10.1016/j.ejmech.2021.113789]

Source

Source(3):

• Scientific Literature
• PubChem BioAssays
• IMI-CARE SARS-CoV-2 Data