ID: ALA295316

Max Phase: Phase

Molecular Formula: C11H8O3

Molecular Weight: 188.18

Molecule Type: Small molecule

Representations

Synonyms (5): Pcur-101 | Plumbagin | NSC-236613 | NSC-688284 | PCUR-101
Synonyms from Alternative Forms(5):

Canonical SMILES:  CC1=CC(=O)c2c(O)cccc2C1=O

Standard InChI:  InChI=1S/C11H8O3/c1-6-5-9(13)10-7(11(6)14)3-2-4-8(10)12/h2-5,12H,1H3

Standard InChI Key:  VCMMXZQDRFWYSE-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: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 188.18

Molecular Weight (Monoisotopic): 188.0473

AlogP: 1.72

#Rotatable Bonds: 0

Polar Surface Area: 54.37

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 3

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.28

CX Basic pKa:

CX LogP: 2.24

CX LogD: 2.18

Aromatic Rings: 1

Heavy Atoms: 14

QED Weighted: 0.67

Np Likeness Score: 1.77

References

1. Lin TS, Zhu LY, Xu SP, Divo AA, Sartorelli AC..  (1991)  Synthesis and antimalarial activity of 2-aziridinyl- and 2,3-bis(aziridinyl)-1,4-naphthoquinonyl sulfonate and acylate derivatives.,  34  (5): [PMID:2033589] [10.1021/jm00109a016]

2. 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]

3. Salmon-Chemin L, Buisine E, Yardley V, Kohler S, Debreu MA, Landry V, Sergheraert C, Croft SL, Krauth-Siegel RL, Davioud-Charvet E..  (2001)  2- and 3-substituted 1,4-naphthoquinone derivatives as subversive substrates of trypanothione reductase and lipoamide dehydrogenase from Trypanosoma cruzi: synthesis and correlation between redox cycling activities and in vitro cytotoxicity.,  44  (4): [PMID:11170645] [10.1021/jm001079l]

4. Salmon-Chemin L, Lemaire A, De Freitas S, Deprez B, Sergheraert C, Davioud-Charvet E..  (2000)  Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi.,  10  (7): [PMID:10762041] [10.1016/s0960-894x(00)00056-1]

5. Gu JQ, Graf TN, Lee D, Chai HB, Mi Q, Kardono LB, Setyowati FM, Ismail R, Riswan S, Farnsworth NR, Cordell GA, Pezzuto JM, Swanson SM, Kroll DJ, Falkinham JO, Wall ME, Wani MC, Kinghorn AD, Oberlies NH..  (2004)  Cytotoxic and antimicrobial constituents of the bark of Diospyros maritima collected in two geographical locations in Indonesia.,  67  (7): [PMID:15270571] [10.1021/np040027m]

6. Santana L, González-Díaz H, Quezada E, Uriarte E, Yáñez M, Viña D, Orallo F..  (2008)  Quantitative structure-activity relationship and complex network approach to monoamine oxidase A and B inhibitors.,  51  (21): [PMID:18834112] [10.1021/jm800656v]

7. Shen CC, Syu WJ, Li SY, Lin CH, Lee GH, Sun CM..  (2002)  Antimicrobial activities of naphthazarins from Arnebia euchroma.,  65  (12): [PMID:12502328] [10.1021/np010599w]

8. Ioset JR, Marston A, Gupta MP, Hostettmann K..  (2000)  Antifungal and larvicidal compounds from the root bark of Cordia alliodora.,  63  (3): [PMID:10757739] [10.1021/np990393j]

9. Sreelatha T, Hymavathi A, Murthy JM, Rani PU, Rao JM, Babu KS..  (2010)  Bioactivity-guided isolation of mosquitocidal constituents from the rhizomes of Plumbago capensis Thunb.,  20  (9): [PMID:20347303] [10.1016/j.bmcl.2010.02.107]

10. Kaur K, Jain M, Kaur T, Jain R..  (2009)  Antimalarials from nature.,  17  (9): [PMID:19299148] [10.1016/j.bmc.2009.02.050]

11. Mortier J, Masereel B, Remouchamps C, Ganeff C, Piette J, Frederick R..  (2010)  NF-kappaB inducing kinase (NIK) inhibitors: identification of new scaffolds using virtual screening.,  20  (15): [PMID:20580552] [10.1016/j.bmcl.2010.06.027]

12. PubChem BioAssay data set, 

13. PubChem BioAssay data set, 

14. Bringmann G, Zhang G, Hager A, Moos M, Irmer A, Bargou R, Chatterjee M..  (2011)  Anti-tumoral activities of dioncoquinones B and C and related naphthoquinones gained from total synthesis or isolation from plants.,  46  (12): [PMID:22019229] [10.1016/j.ejmech.2011.09.012]

15. PubChem BioAssay data set, 

16. Dandawate P, Khan E, Padhye S, Gaba H, Sinha S, Deshpande J, Venkateswara Swamy K, Khetmalas M, Ahmad A, Sarkar FH..  (2012)  Synthesis, characterization, molecular docking and cytotoxic activity of novel plumbagin hydrazones against breast cancer cells.,  22  (9): [PMID:22483392] [10.1016/j.bmcl.2012.03.060]

17. Whitson EL, Sun H, Thomas CL, Henrich CJ, Sayers TJ, McMahon JB, Griesinger C, McKee TC..  (2012)  Synergistic TRAIL sensitizers from Barleria alluaudii and Diospyros maritima.,  75  (3): [PMID:22313254] [10.1021/np200805z]

18. Kawiak A, Zawacka-Pankau J, Lojkowska E..  (2012)  Plumbagin induces apoptosis in Her2-overexpressing breast cancer cells through the mitochondrial-mediated pathway.,  75  (4): [PMID:22512718] [10.1021/np3000409]

19. Lupescu A, Jilani K, Zbidah M, Lang E, Lang F..  (2012)  Enhanced Ca2+ entry, ceramide formation, and apoptotic death of erythrocytes triggered by plumbagin.,  75  (11): [PMID:23110447] [10.1021/np300611r]

20. Brunhofer G, Fallarero A, Karlsson D, Batista-Gonzalez A, Shinde P, Gopi Mohan C, Vuorela P..  (2012)  Exploration of natural compounds as sources of new bifunctional scaffolds targeting cholinesterases and beta amyloid aggregation: the case of chelerythrine.,  20  (22): [PMID:23062825] [10.1016/j.bmc.2012.09.040]

21. Fischer TC, Gosch C, Mirbeth B, Gselmann M, Thallmair V, Stich K..  (2012)  Potent and specific bactericidal effect of juglone (5-hydroxy-1,4-naphthoquinone) on the fire blight pathogen Erwinia amylovora.,  60  (49): [PMID:23163769] [10.1021/jf303584r]

22. Rajendra Prasad K, Suresh Babu K, Ranga Rao R, Suresh G, Rekha K, Madhusudana Murthy J, Usha Rani P, Madhusudana Rao J.  (2012)  Synthesis and insect antifeedant activity of plumbagin derivatives,  21  (5): [10.1007/s00044-011-9559-7]

23. Akhtar Y, Isman MB, Niehaus LA, Lee CH, Lee HS..  (2012)  Antifeedant and toxic effects of naturally occurring and synthetic quinones to the cabbage looper, Trichoplusia ni,  31  (1): [10.1016/j.cropro.2011.09.009]

24. Sreelatha T, Hymavathi A, Babu KS, Murthy JM, Pathipati UR, Rao JM..  (2009)  Synthesis and insect antifeedant activity of plumbagin derivatives with the amino acid moiety.,  57  (14): [PMID:19530696] [10.1021/jf901760h]

25. Muriuki B, Midiwo JO, Mbugua PM, Keriko JM.  (2013)  The antimycobacterial MICs, SARs, and QSARs of some ethnobotanically selected phytocompounds,  22  (11): [10.1007/s00044-013-0485-8]

26. Pile JE, Navalta JW, Davis CD, Sharma NC..  (2013)  Interventional effects of plumbagin on experimental ulcerative colitis in mice.,  76  (6): [PMID:23742275] [10.1021/np3008792]

27. 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]

28. Sridhar J, Sfondouris ME, Bratton MR, Nguyen TL, Townley I, Klein Stevens CL, Jones FE..  (2014)  Identification of quinones as HER2 inhibitors for the treatment of trastuzumab resistant breast cancer.,  24  (1): [PMID:24355130] [10.1016/j.bmcl.2013.11.064]

29. Dandawate P, Ahmad A, Deshpande J, Swamy KV, Khan EM, Khetmalas M, Padhye S, Sarkar F..  (2014)  Anticancer phytochemical analogs 37: synthesis, characterization, molecular docking and cytotoxicity of novel plumbagin hydrazones against breast cancer cells.,  24  (13): [PMID:24835626] [10.1016/j.bmcl.2014.04.100]

30. Mallavadhani UV, Prasad CV, Shrivastava S, Naidu VG..  (2014)  Synthesis and anticancer activity of some novel 5,6-fused hybrids of juglone based 1,4-naphthoquinones.,  83  [PMID:24953027] [10.1016/j.ejmech.2014.06.012]

31. Raghu D, Karunagaran D..  (2014)  Plumbagin downregulates Wnt signaling independent of p53 in human colorectal cancer cells.,  77  (5): [PMID:24828199] [10.1021/np4010085]

32. Jones P.  (2012)  Development of second generation epigenetic agents,  3  (2): [10.1039/C1MD00199J]

33. Dandawate P, Vemuri K, Venkateswara Swamy K, Khan EM, Sritharan M, Padhye S..  (2014)  Synthesis, characterization, molecular docking and anti-tubercular activity of Plumbagin-Isoniazid Analog and its β-cyclodextrin conjugate.,  24  (21): [PMID:25264074] [10.1016/j.bmcl.2014.09.032]

34. Sreelatha T, Kandhasamy S, Dinesh R, Shruthy S, Shweta S, Mukesh D, Karunagaran D, Balaji R, Mathivanan N, Perumal PT..  (2014)  Synthesis and SAR study of novel anticancer and antimicrobial naphthoquinone amide derivatives.,  24  (15): [PMID:24913712] [10.1016/j.bmcl.2014.04.080]

35. Fiorito S, Genovese S, Taddeo VA, Mathieu V, Kiss R, Epifano F..  (2016)  Novel juglone and plumbagin 5-O derivatives and their in vitro growth inhibitory activity against apoptosis-resistant cancer cells.,  26  (2): [PMID:26706169] [10.1016/j.bmcl.2015.12.017]

36. Simon RP, Robaa D, Alhalabi Z, Sippl W, Jung M..  (2016)  KATching-Up on Small Molecule Modulators of Lysine Acetyltransferases.,  59  (4): [PMID:26701186] [10.1021/acs.jmedchem.5b01502]

37. Haranahalli K, Tong S, Ojima I..  (2016)  Recent advances in the discovery and development of antibacterial agents targeting the cell-division protein FtsZ.,  24  (24): [PMID:27189886] [10.1016/j.bmc.2016.05.003]

38. Kang CG, Im E, Lee HJ, Lee EO..  (2017)  Plumbagin reduces osteopontin-induced invasion through inhibiting the Rho-associated kinase signaling pathway in A549 cells and suppresses osteopontin-induced lung metastasis in BalB/c mice.,  27  (9): [PMID:28359791] [10.1016/j.bmcl.2017.03.047]

39. Bao N, Ou J, Xu M, Guan F, Shi W, Sun J, Chen L..  (2017)  Novel NO-releasing plumbagin derivatives: Design, synthesis and evaluation of antiproliferative activity.,  137  [PMID:28558333] [10.1016/j.ejmech.2017.05.046]

40. Jardim GAM, Silva TL, Goulart MOF, de Simone CA, Barbosa JMC, Salomão K, de Castro SL, Bower JF, da Silva Júnior EN..  (2017)  Rhodium-catalyzed C-H bond activation for the synthesis of quinonoid compounds: Significant Anti-Trypanosoma cruzi activities and electrochemical studies of functionalized quinones.,  136  [PMID:28521262] [10.1016/j.ejmech.2017.05.011]

41. Bao N, Ou J, Li N, Zou P, Sun J, Chen L..  (2018)  Novel anticancer hybrids from diazen-1-ium-1,2-diolate nitric oxide donor and ROS inducer plumbagin: Design, synthesis and biological evaluations.,  154  [PMID:29772386] [10.1016/j.ejmech.2018.04.047]

42. Li K, Yang K, Zheng L, Li Y, Wang Q, Lin R, He D..  (2018)  Anti-acute myeloid leukemia activity of 2-chloro-3-alkyl-1,4-naphthoquinone derivatives through inducing mtDNA damage and GSH depletion.,  26  (14): [PMID:30007564] [10.1016/j.bmc.2018.07.010]

43. Joshi P, Sonawane VR, Williams IS, McCann GJP, Gatchie L, Sharma R, Satti N, Chaudhuri B, Bharate SB..  (2018)  Identification of karanjin isolated from the Indian beech tree as a potent CYP1 enzyme inhibitor with cellular efficacy via screening of a natural product repository.,  9  (2): [PMID:30108931] [10.1039/C7MD00388A]

44. Schepetkin IA, Karpenko AS, Khlebnikov AI, Shibinska MO, Levandovskiy IA, Kirpotina LN, Danilenko NV, Quinn MT..  (2019)  Synthesis, anticancer activity, and molecular modeling of 1,4-naphthoquinones that inhibit MKK7 and Cdc25.,  183  [PMID:31563013] [10.1016/j.ejmech.2019.111719]

45. 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]

46. Kawiak A, Domachowska A, Lojkowska E..  (2019)  Plumbagin Increases Paclitaxel-Induced Cell Death and Overcomes Paclitaxel Resistance in Breast Cancer Cells through ERK-Mediated Apoptosis Induction.,  82  (4): [PMID:30810041] [10.1021/acs.jnatprod.8b00964]

47. Huang M, Huang J, Zheng Y, Sun Q..  (2019)  Histone acetyltransferase inhibitors: An overview in synthesis, structure-activity relationship and molecular mechanism.,  178  [PMID:31195169] [10.1016/j.ejmech.2019.05.078]

48. Hill K, Fiorito S, Taddeo VA, Schulze A, Leonhardt M, Epifano F, Genovese S..  (2016)  Plumbagin, Juglone, and Boropinal as Novel TRPA1 Agonists.,  79  (4): [PMID:26905390] [10.1021/acs.jnatprod.5b00396]

49. Unpublished dataset, 

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

51. Patel OPS, Jesumoroti OJ, Legoabe LJ, Beteck RM..  (2021)  Metronidazole-conjugates: A comprehensive review of recent developments towards synthesis and medicinal perspective.,  210  [PMID:33234343] [10.1016/j.ejmech.2020.112994]

52. Shen CC, Afraj SN, Hung CC, Barve BD, Kuo LY, Lin ZH, Ho HO, Kuo YH..  (2021)  Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives.,  41  [PMID:33766765] [10.1016/j.bmcl.2021.127976]

53. Norman EO, Tuohey H, Pizzi D, Saidah M, Bell R, Brkljača R, White JM, Gasser RB, Taki AC, Urban S..  (2021)  Phytochemical Profiling and Biological Activity of the Australian Carnivorous Plant, Drosera magna.,  84  (4.0): [PMID:33631073] [10.1021/acs.jnatprod.0c00869]

54. Lei Y, Li Y, Tan Y, Qian Z, Zhou Q, Jia D, Sun Q..  (2021)  Novel Mechanistic Observations and NES-Binding Groove Features Revealed by the CRM1 Inhibitors Plumbagin and Oridonin.,  84  (5.0): [PMID:33890470] [10.1021/acs.jnatprod.0c01231]

55. Huecas S, Araújo-Bazán L, Ruiz FM, Ruiz-Ávila LB, Martínez RF, Escobar-Peña A, Artola M, Vázquez-Villa H, Martín-Fontecha M, Fernández-Tornero C, López-Rodríguez ML, Andreu JM..  (2021)  Targeting the FtsZ Allosteric Binding Site with a Novel Fluorescence Polarization Screen, Cytological and Structural Approaches for Antibacterial Discovery.,  64  (9.0): [PMID:33908781] [10.1021/acs.jmedchem.0c02207]

56. Liu S, Qiao W, Sun Q, Luo Y..  (2021)  Chromosome Region Maintenance 1 (XPO1/CRM1) as an Anticancer Target and Discovery of Its Inhibitor.,  64  (21.0): [PMID:34669417] [10.1021/acs.jmedchem.1c01145]

57. Mahanty S, Rathinasamy K..  (2021)  The natural anthraquinone dye purpurin exerts antibacterial activity by perturbing the FtsZ assembly.,  50  [PMID:34700238] [10.1016/j.bmc.2021.116463]

58. Shagufta, Ahmad I..  (2023)  Therapeutic significance of molecular hybrids for breast cancer research and treatment.,  14  (2): [PMID:36846377] [10.1039/d2md00356b]

Source

Source(4):

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