Six indirubin derivatives have been synthesized and their inhibitory effects on the growth of HL-60 human promyelocytic leukemia cells investigated. Cell viability was determined using the trypan blue exclusion method. Indirubin-3′-oxime (I-1) inhibited the growth of HL-60 cells with a GI50 value of 36.6 μM, whereas I-0, I-2, I-3, I-4 and I-6 showed only weak cytotoxic activities against HL-60 cancer cells with GI50 values in the range of 97.3 to over 100 μM. These results indicate that indirubin derivatives might be useful candidate agents for exploring potential antileukemic drugs.
LaurentM, NicoleG, LeandrosAS, GerhardE. (2006) Indirubin: the red shade of indigo. Life Progress Editions, Roscoff, France, 135–156.
6.
HoesselR, LeclercS, EndicottJA, NobelM, LawrieA, TunnahP, LeostM, DamiensE, MarieD, MarkoD, NiederbergerE, TangW, EisenbrandG, MeijerL. (1999) Indirubin, the active constituent of a Chinese antileukaemia medicine, inhibits cyclin dependent kinases. Natural Cell Biology, 1, 60–67.
7.
ChunrongY, MohamedR, YunD, DanielC, GeoffreyK, PaulD, StevenG. (2003) The lethal effects of pharmacological cyclin-dependent kinase inhibitors in human leukemia cells proceed through a phosphatidylinositol 3-kinase/Akt-dependent process 1. Cancer Research, 63, 1822–1833.
8.
SchnitzerSE, SchmidtT, ZhouJ, EisenbrandG, BruneB. (2005) Inhibition of GSK3β by indirubins restores HIF-1α accumulation under prolonged periods of hypoxia/anoxia. FEBS Letters, 79, 529–533.
NamS, BuettnerR, TurksonJ, KimD, ChengJQ, MuehlbeyerS, HippeF, VatterS, MerzKH, EisenbrandG, JoveR. (2005) Indirubin derivatives inhibit Stat3 signaling and induce apoptosis in human cancer cells. Proceeding of National Academy of Sciences USA, 102, 5998–6003.
11.
ZhenY, SorensenV, JinY, SuoZ, WiedlochaA. (2007) Indirubin-3′-monoxime inhibits autophosphorylation of FGFR1 and stimulates ERK1/2 activity via p38 MAPK. Oncogene, 26, 3672–3685.
12.
AdachiJ, MoriY, MatsuiS, TakigamiH, FujinoJ, KitagawaH, MillerCA, KatoT, SaekiK, MatsudaT. (2001) Indirubin and indigo are potent aryl hydrocarbon receptor ligands present in human urine. Journal of Biological Chemistry, 276, 31475–31478.
13.
SuzukiK, AdachiR, HirayamaA, WatanabeH, OtaniS, WatanabeY, KasaharaT. (2005) Indirubin, a Chinese antileukaemia drug, promotes neutrophilic differentiation of human myelocytic leukaemia HL-60 cells. British Journal of Haematology, 130, 681–690.
14.
KimSH, KimSW, ChoiSJ, KimYC, KimTS. (2006) Enhancing effect of indirubin derivatives on 1,25-dihydroxyvitamin D3- and all-trans retinoic acid-induced differentiation of HL-60 leukemia cells. Bioorganic Medicinal Chemistry, 14, 6752–6758.
15.
Kagialis-GirardS, MialouV, ChebelA, ChienWW, TigaudI, MokdadF, BadiouC, FfrenchM. (2007) Inhibition of normal lymphocyte proliferation by indirubin-3′-monoxime: a multifactorial process. Leukemia Lymphoma, 48, 605–615.
16.
CuongNM, ThuyDT T, HaNV, TaiBH. (2007) Isolation of indirubin from the leaves of Strobilanthes cusia. Journal of Science and Technology, 45 (3A), 195–199.
17.
BHTai, DHHoan, CuongNM. (2009) Study on the acetylation and NMR reassignment of indirubin derivatives. Natural Product Research, in press.
18.
FreshneyRI. (1987) Culture of Animal Cells: A Manual of Basic Technique. Alan R. Liss, Inc., New York, USA, p. 117.
