ID: ALA9470

Max Phase: Preclinical

Molecular Formula: C16H16O5

Molecular Weight: 288.30

Molecule Type: Small molecule

Representations

Canonical SMILES:  CC(C)=CC[C@@H](O)C1=CC(=O)c2c(O)ccc(O)c2C1=O

Standard InChI:  InChI=1S/C16H16O5/c1-8(2)3-4-10(17)9-7-13(20)14-11(18)5-6-12(19)15(14)16(9)21/h3,5-7,10,17-19H,4H2,1-2H3/t10-/m1/s1

Standard InChI Key:  NEZONWMXZKDMKF-SNVBAGLBSA-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: 288.30

Molecular Weight (Monoisotopic): 288.0998

AlogP: 2.12

#Rotatable Bonds: 3

Polar Surface Area: 94.83

Molecular Species: NEUTRAL

HBA: 5

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.50

CX Basic pKa:

CX LogP: 3.01

CX LogD: 2.98

Aromatic Rings: 1

Heavy Atoms: 21

QED Weighted: 0.58

Np Likeness Score: 2.15

References

1. Ahn BZ, Baik KU, Kweon GR, Lim K, Hwang BD..  (1995)  Acylshikonin analogues: synthesis and inhibition of DNA topoisomerase-I.,  38  (6): [PMID:7699697] [10.1021/jm00006a025]

2. Lu Q, Liu W, Ding J, Cai J, Duan W..  (2002)  Shikonin derivatives: synthesis and inhibition of human telomerase.,  12  (10): [PMID:11992780] [10.1016/s0960-894x(02)00158-0]

3. 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]

4. Shrestha S, Shim YS, Kim KC, Lee KH, Cho H..  (2004)  Evans Blue and other dyes as protein tyrosine phosphatase inhibitors.,  14  (8): [PMID:15050628] [10.1016/j.bmcl.2004.01.079]

5. An S, Park YD, Paik YK, Jeong TS, Lee WS..  (2007)  Human ACAT inhibitory effects of shikonin derivatives from Lithospermum erythrorhizon.,  17  (4): [PMID:17157006] [10.1016/j.bmcl.2006.11.024]

6. Tanaka S, Tajima M, Tsukada M, Tabata M..  (1986)  A comparative study on anti-inflammatory activities of the enantiomers, shikonin and alkannin.,  49  (3): [PMID:3760886] [10.1021/np50045a014]

7. Tanaka S, Tajima M, Tsukada M, Tabata M..  (1986)  A comparative study on anti-inflammatory activities of the enantiomers, shikonin and alkannin.,  49  (3): [PMID:3760886] [10.1021/np50045a014]

8. Honda G, Sakakibara F, Yazaki K, Tabata M..  (1988)  Isolation of deoxyshikonin, an antidermatophytic principle from Lithospermum erythrorhizon cell cultures.,  51  (1): [PMID:3373224] [10.1021/np50055a025]

9. Cui XR, Tsukada M, Suzuki N, Shimamura T, Gao L, Koyanagi J, Komada F, Saito S..  (2008)  Comparison of the cytotoxic activities of naturally occurring hydroxyanthraquinones and hydroxynaphthoquinones.,  43  (6): [PMID:17949858] [10.1016/j.ejmech.2007.08.009]

10. 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]

11. Wang W, Dai M, Zhu C, Zhang J, Lin L, Ding J, Duan W..  (2009)  Synthesis and biological activity of novel shikonin analogues.,  19  (3): [PMID:19111464] [10.1016/j.bmcl.2008.12.032]

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. Zhao LM, Xie TP, He YQ, Xu DF, Li SS..  (2009)  Synthesis and antitumor activity of 6- and 2-(1-substituted-thio-4-methylpent-3-enyl)-5,8-dimethoxynaphthalene-1,4-diones.,  44  (4): [PMID:18996624] [10.1016/j.ejmech.2008.09.039]

14. Su Y, Xie J, Wang Y, Hu X, Lin X..  (2010)  Synthesis and antitumor activity of new shikonin glycosides.,  45  (7): [PMID:20403646] [10.1016/j.ejmech.2010.02.002]

15. PubChem BioAssay data set, 

16. Zhou W, Peng Y, Li SS..  (2010)  Semi-synthesis and anti-tumor activity of 5,8-O-dimethyl acylshikonin derivatives.,  45  (12): [PMID:20970893] [10.1016/j.ejmech.2010.09.068]

17. Zhou W, Zhang X, Xiao L, Ding J, Liu QH, Li SS..  (2011)  Semi-synthesis and antitumor activity of 6-isomers of 5, 8-O-dimethyl acylshikonin derivatives.,  46  (8): [PMID:21620530] [10.1016/j.ejmech.2011.05.006]

18. Kim JY, Jeong HJ, Park JY, Kim YM, Park SJ, Cho JK, Park KH, Ryu YB, Lee WS..  (2012)  Selective and slow-binding inhibition of shikonin derivatives isolated from Lithospermum erythrorhizon on glycosyl hydrolase 33 and 34 sialidases.,  20  (5): [PMID:22300884] [10.1016/j.bmc.2012.01.011]

19. He H, Bai LP, Jiang ZH..  (2012)  Synthesis and human telomeric G-quadruplex DNA-binding activity of glucosaminosides of shikonin/alkannin.,  22  (4): [PMID:22281188] [10.1016/j.bmcl.2011.12.143]

20. Derbyshire ER, Prudêncio M, Mota MM, Clardy J..  (2012)  Liver-stage malaria parasites vulnerable to diverse chemical scaffolds.,  109  (22): [PMID:22586124] [10.1073/pnas.1118370109]

21. 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]

22. 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]

23. LI C, FUKUSHI Y, KAWABATA J, TAHARA S, MIZUTANI J, UYEDA I.  (1998)  Antiviral and Antifungal Activities of Some Naphthoquinones Isolated from the Roots of Lithospermum erythrorhizon,  23  (1): [10.1584/jpestics.23.54]

24. Genomics of Drug Sensitity in Cancer screening data, Wellcome Trust Sanger Institute,  [10.6019/CHEMBL1201861]

25. Kornienko A, Mathieu V, Rastogi SK, Lefranc F, Kiss R..  (2013)  Therapeutic agents triggering nonapoptotic cancer cell death.,  56  (12): [PMID:23517069] [10.1021/jm400136m]

26. Wang R, Zhang X, Song H, Zhou S, Li S..  (2014)  Synthesis and evaluation of novel alkannin and shikonin oxime derivatives as potent antitumor agents.,  24  (17): [PMID:25127868] [10.1016/j.bmcl.2014.07.012]

27. Zhao LM, Cao FX, Jin HS, Zhang JH, Szwaya J, Wang G..  (2016)  One-pot synthesis of 1,4-dihydroxy-2-((E)-1-hydroxy-4-phenylbut-3-enyl)anthracene-9,10-diones as novel shikonin analogs and evaluation of their antiproliferative activities.,  26  (11): [PMID:27080175] [10.1016/j.bmcl.2016.04.006]

28. Ning X, Qi H, Li R, Li Y, Jin Y, McNutt MA, Liu J, Yin Y..  (2017)  Discovery of novel naphthoquinone derivatives as inhibitors of the tumor cell specific M2 isoform of pyruvate kinase.,  138  [PMID:28688274] [10.1016/j.ejmech.2017.06.064]

29. Hou X, Wang M, Wen Y, Ni T, Guan X, Lan L, Zhang N, Zhang A, Yang CG..  (2018)  Quinone skeleton as a new class of irreversible inhibitors against Staphylococcus aureus sortase A.,  28  (10): [PMID:29650293] [10.1016/j.bmcl.2018.04.005]

30. Huang G, Zhao HR, Meng QQ, Zhang QJ, Dong JY, Zhu BQ, Li SS..  (2018)  Synthesis and biological evaluation of sulfur-containing shikonin oxime derivatives as potential antineoplastic agents.,  143  [PMID:29174813] [10.1016/j.ejmech.2017.11.031]

31. You L, Zhu H, Wang C, Wang F, Li Y, Li Y, Wang Y, He B..  (2017)  Scutellarin inhibits Hela cell growth and glycolysis by inhibiting the activity of pyruvate kinase M2.,  27  (24): [PMID:29157862] [10.1016/j.bmcl.2017.11.011]

32. Lin HY, Han HW, Sun WX, Yang YS, Tang CY, Lu GH, Qi JL, Wang XM, Yang YH..  (2018)  Design and characterization of α-lipoic acyl shikonin ester twin drugs as tubulin and PDK1 dual inhibitors.,  144  [PMID:29268130] [10.1016/j.ejmech.2017.12.019]

33. Ning X, Li Y, Qi H, Li R, Jin Y, Liu J, Yin Y..  (2018)  Anti-cancer effect of a novel 2,3-didithiocarbamate-substituted naphthoquinone as a tumor metabolic suppressor in vitro and in vivo.,  9  (4): [PMID:30108954] [10.1039/C8MD00062J]

34. Park JY, Park DH, Jeon Y, Kim YJ, Lee J, Shin MS, Kang KS, Hwang GS, Kim HY, Yamabe N..  (2018)  Eupatilin inhibits angiogenesis-mediated human hepatocellular metastasis by reducing MMP-2 and VEGF signaling.,  28  (19): [PMID:30177376] [10.1016/j.bmcl.2018.08.034]

35. 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]

36. Liu Y, Liang Y, Jiang J, Qin Q, Wang L, Liu X..  (2019)  Design, synthesis and biological evaluation of 1,4-dihydroxyanthraquinone derivatives as anticancer agents.,  29  (9): [PMID:30846253] [10.1016/j.bmcl.2019.02.026]

37. Zhang L, Xu Z..  (2019)  Coumarin-containing hybrids and their anticancer activities.,  181  [PMID:31404864] [10.1016/j.ejmech.2019.111587]

38. Sun WX, Han HW, Yang MK, Wen ZL, Wang YS, Fu JY, Lu YT, Wang MY, Bao JX, Lu GH, Qi JL, Wang XM, Lin HY, Yang YH..  (2019)  Design, synthesis and biological evaluation of benzoylacrylic acid shikonin ester derivatives as irreversible dual inhibitors of tubulin and EGFR.,  27  (23): [PMID:31648877] [10.1016/j.bmc.2019.115153]

39. Huang G, Dong JY, Zhang QJ, Meng QQ, Zhao HR, Zhu BQ, Li SS..  (2019)  Discovery and synthesis of sulfur-containing 6-substituted 5,8-dimethoxy-1,4-naphthoquinone oxime derivatives as new and potential anti-MDR cancer agents.,  165  [PMID:30677614] [10.1016/j.ejmech.2019.01.005]

40. Min W, Hou Z, Zhang F, Xie S, Yuan K, Dong H, Wang L, Qi L, Luo C, Ding H, Yang P..  (2020)  Computational discovery and biological evaluation of novel inhibitors targeting histone-lysine N-methyltransferase SET7.,  28  (7): [PMID:32088124] [10.1016/j.bmc.2020.115372]

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

42. Gil C,Ginex T,Maestro I,Nozal V,Barrado-Gil L,Cuesta-Geijo MÁ,Urquiza J,Ramírez D,Alonso C,Campillo NE,Martinez A.  (2020)  COVID-19: Drug Targets and Potential Treatments.,  63  (21): [PMID:32511912] [10.1021/acs.jmedchem.0c00606]

43. Shao YY,Yin Y,Lian BP,Leng JF,Xia YZ,Kong LY.  (2020)  Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site.,  190  [PMID:32035399] [10.1016/j.ejmech.2020.112105]

44. O'Donnell HR, Tummino TA, Bardine C, Craik CS, Shoichet BK..  (2021)  Colloidal Aggregators in Biochemical SARS-CoV-2 Repurposing Screens.,  64  (23.0): [PMID:34812616] [10.1021/acs.jmedchem.1c01547]

45. 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]

46. Amin SA, Banerjee S, Ghosh K, Gayen S, Jha T..  (2021)  Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors.,  29  [PMID:33191083] [10.1016/j.bmc.2020.115860]

47. Han H, He C, Chen X, Luo Y, Yang M, Wen Z, Hu J, Lin F, Han M, Yin T, Yang R, Lin H, Qi J, Yang Y..  (2022)  Shikonin N-benzyl matrinic acid ester derivatives as novel telomerase inhibitors with potent activity against lung cancer cell lines.,  57  [PMID:34922028] [10.1016/j.bmcl.2021.128503]

48. Arora S, Joshi G, Chaturvedi A, Heuser M, Patil S, Kumar R..  (2022)  A Perspective on Medicinal Chemistry Approaches for Targeting Pyruvate Kinase M2.,  65  (2.0): [PMID:34726055] [10.1021/acs.jmedchem.1c00981]

49. Valipour M..  (2022)  Recent advances of antitumor shikonin/alkannin derivatives: A comprehensive overview focusing on structural classification, synthetic approaches, and mechanisms of action.,  235  [PMID:35367708] [10.1016/j.ejmech.2022.114314]

50. Rathod B, Chak S, Patel S, Shard A..  (2021)  Tumor pyruvate kinase M2 modulators: a comprehensive account of activators and inhibitors as anticancer agents.,  12  (7.0): [PMID:34355179] [10.1039/D1MD00045D]

51. Yang H, Yang J..  (2021)  A review of the latest research on M^pro targeting SARS-COV inhibitors.,  12  (7.0): [PMID:34355175] [10.1039/D1MD00066G]

52. Shagufta, Ahmad I..  (2021)  The race to treat COVID-19: Potential therapeutic agents for the prevention and treatment of SARS-CoV-2.,  213  [PMID:33486200] [10.1016/j.ejmech.2021.113157]

53. Wasilewicz A, Kirchweger B, Bojkova D, Abi Saad MJ, Langeder J, Bütikofer M, Adelsberger S, Grienke U, Cinatl J, Petermann O, Scapozza L, Orts J, Kirchmair J, Rabenau HF, Rollinger JM..  (2023)  Identification of Natural Products Inhibiting SARS-CoV-2 by Targeting Viral Proteases: A Combined in Silico and in Vitro Approach.,  86  (2.0): [PMID:36651644] [10.1021/acs.jnatprod.2c00843]

54. Amin SA, Jha T..  (2020)  Fight against novel coronavirus: A perspective of medicinal chemists.,  201  [PMID:32563814] [10.1016/j.ejmech.2020.112559]

55. Tao Y, Hao X, Ding X, Cherukupalli S, Song Y, Liu X, Zhan P..  (2020)  Medicinal chemistry insights into novel CDC25 inhibitors.,  201  [PMID:32603979] [10.1016/j.ejmech.2020.112374]

Source

Source(5):

• Scientific Literature
• Sanger Institute Genomics of Drug Sensitivity in Cancer
• PubChem BioAssays
• Harvard Malaria Screening
• IMI-CARE SARS-CoV-2 Data