Table 1.
Anti-acute myeloid leukemia (AML) naphthoquinones.
| Structure | AML Cell Lines | IC50 (μM) | In Vivo | References |
|---|---|---|---|---|
| Mono- or di-substituted monomeric naphthoquinones | ||||
Menadione 2-methyl-1,4-naphthoquinone |
HL-60, U937 | Not reported directly | Not tested | Yeo HS, et al. 2012 |
Juglone 5-hydroxyl-1,4-naphthoquinone |
HL-60 | 8 | Not tested | Xu HL, et al., 2010 |
Lawsone 2-hydroxyl-1,4-naphthoquinone |
HL-60 | >50 | Not tested | Esteves-Souza A, et al., 2008 |
2-glycinyl-1,4-naphthoquinone |
HL-60 | 3 | Not tested | de Moraes TA, et al., 2014 |
Plumbagin 5-hydroxy-2-methyl-1,4-naphthoquinone |
Kasumi-1, HL-60, U937 | 0.6–1.4 | Activity: Tumor volume reduction Tolerability: No significant weight loss, tissue damage or behavior change (Xu KH, et al.) |
Kawiak A, et al., 2007 Xu KH, et al., 2010 Gaascht F, et al., 2014 Kong X, et al., 2017 Zhang J, et al., 2017 |
Lapachol 2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone |
Kasumi-1 Primary cells from patients HL-60 |
Not reported directly >50 |
Not tested | de Souza Reis FR, et al., 2013 Esteves-Souza A, et al., 2008 |
Atovaquone trans -2-[4-(4-chlorophenyl)cyclohexyl]-3-hydroxy-1,4-naphthalenedione |
MOLM13, MV4-11, THP-1, NB4, Kasumi-1, HL-60, KG1, HEL | 13.7–98.9 | Decreased diseased burden and prolonged survival in the treatment group compared to the control group (Stevens AM, et al.) | Xiang M, et al., 2016 Stevens AM, et al., 2017 |
2-((4-((3-aminopropyl)(benzyl)amino)butyl) amino)naphthalene-1,4-dione |
HL-60 | 10.5 | Not tested | Esteves-Souza A, et al., 2008 |
Ramentaceone 7-Methyljuglone |
HL-60 | 8.8 | Not tested | Kawiak A, et al., 2012 |
Cordiaquinone J |
HL-60 | 2.7 | Not tested | Marinho-Filho JD., et al., 2010 |
TW-92 2-chloro-3-(3-amino-4-methyl-phenylamino)-1,4-naphthoquinone |
U937, peripheral blood mononuclear cells from AML patients | 3.2 | Not tested | Hallak M, et al., 2009 |
| Multi-substituted monomeric naphthoquinones | ||||
Shikonin 5,8-dihydroxy-2[(1R)-hydroxy-4-methylpent-3-en-1-yl]-3-methyl-1,4-naphthoquinone |
HL-60, U937, primary AML cells |
3.8 | Prolonged survival observed in the treatment group compared to the control group (Yang H, et al.) | Yang H, et al., 2009 Zhang B, et al. 2012 Zhao Q, et al., 2015 Trivedi, et al., 2016 |
SH-7 1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enylfuran-2-caroxylate |
HL-60 | 2 | Not tested | Yang F, et al., 2006 |
5,8-dihydroxy-2-(1-hydroxy-2-nitroethyl)-1,4-naphthoquinone |
HL-60 | 0.14 | Not tested | Beretta GL, et al., 2017 |
3-butyl-2-chloro-5,7-dimethoxy-1,4-naphthoquinone |
HL-60 | 3.8 | Not tested | Li K, et al., 2018 |
| Heterocyclic monomeric naphthoquinones | ||||
FNQ3 (Furanonaphthquinone) 2-Methylnaphtho[2–b]furan-4,9-dione |
HL60, NB-4, U937, THP1, primary AML cells | 5.9–8.2 | Not tested | Desmond JC, et al., 2005 |
FN6-one (Furonaphthoquinone) |
HL-60, U937 | 0.87–3.0 | Not tested | Inagaki R, et al., 2013 |
Nor-β-lapachone |
HL-60, KG1, K562 | 0.4–17.2 | Not tested | da Silva EN Jr, et al. 2007, 2010 Cavalcanti, et al., 2011 Araújo AJ, et al., 2012 Cardoso, et al., 2014 |
β-lapachone 3,4-dihydro-2,2-dimethyl-2H-naphtho[1–b]pyran-5,6-dione |
HL-60 | 7.1 | Not tested | Planchon SM, et al., 1995, 1999 da Silva EN Jr, et al. 2007, 2010 Inagaki, et al., 2015 |
Dunnione |
HL-60 | 0.9 | Not tested | Inagaki, et al., 2015 |
LQB-118 (pterocarpanquinone) |
HL60, U937, Kasumi-1 |
6–9 | Non-cytotoxic to normal BM cells in healthy control mice. | de Souza Reis, et al., 2013, Nestal De Moraes, et al., 2014 |
| Dimeric naphthoquinones | ||||
3-bromo-3′-hydroxyl-dimeric 1,4-naphthoquinone |
MOLM-14, THP-1, primary AML cells | 0.36–8.5 | Tested for tolerability and side effects with IP and SC injections. | Lapidus, et al., 2016 |
3,3′-bis-aziridinyl-dimeric 1,4-naphthoquinone |
MOLM-14, THP-1, primary AML cells | 0.18–2 | Tested for tolerability with IP injections. | Carter-Cooper, et al., 2017 |
BM = bone marrow, IP = intraperitoneally, SC = subcutaneously.