RESUMEN
A new series of ortho-naphthoquinone analogs of ß-lapachone were designed, synthesized and evaluated. The biological results indicated that most of our compounds were efficient substrates for NQO1. The new scaffold with water-soluble side chain resulted in greater solubility under acidic condition compared to ß-lapachone. Thus avoiding the use of hydroxylpropyl ß-cyclodextrin which would finally cause the rapid drug clearance from the blood and dose-limiting toxicity in the form of hemolytic anemia. The most soluble and promising compound in this series was 2-((4-benzylpiperazin-1-yl)methyl)naphtho[2,1-d]oxazole-4,5-dione (3k), which inhibited cancer cell (NQO1-rich A549 cell line) growth at IC50 values of 4.6±1.0µmol·L(-1). Furthermore, compound 3k had in vivo antitumor activity in an A549 tumor xenografts mouse model comparable to the activity obtained with ß-lapachone. The results indicated that these ortho-naphthoquinones could serve as promising leads for further optimization as novel substrates for NQO1.
Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Naftoquinonas/química , Naftoquinonas/uso terapéutico , Animales , Antineoplásicos/síntesis química , Línea Celular Tumoral , Humanos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , Ratones Desnudos , Simulación del Acoplamiento Molecular , Naftoquinonas/síntesis química , Naftoquinonas/metabolismo , Solubilidad , Agua/químicaRESUMEN
OBJECTIVE: To observe the effects of Chinese decoction and ligustrazin hydrochloride injection combined with He-Ne laser on lipoperoxide (LPO) and Superoxide dismutase (SOD) in patients with chloasma. METHODS: 90 cases of chloasma were randomly divided into the following two groups: a treatment group (of 54 cases) treated by a self-prepared prescription for toning the kidneys and relieving the depressed liver to remove blood stasis, ligustrazin hydrochloricde injection and He-Ne laser therapy, and a control group (of 36 cases) treated with oral administration of Vitamin E and Vitamin C plus external application of 20% Azelaic acid cream. RESULTS: The total effective rate in the treatment group was 79.6%, which was significantly higher than that of the control group (P < 0.05). After treatment, the LPO level in the treatment group was significantly lowered (P < 0.01), and the SOD level was significantly elevated (P < 0.05). CONCLUSION: The therapeutic methods adopted in the treatment group may show the action of antioxidation, providing good clinical effects for treating chloasma.