Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-03-09
1997-09-02
Goldberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61R 3134
Patent
active
056631979
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to a novel compound possessing antitumor activity, and an antitumor agent comprising said compound.
The mortality from cancers continues to increase every year, and cancers are major causes of deaths in advanced countries. Control of cancers is therefore the greatest interest in the medical field. Development of antitumor agents has been one of the important themes for cancer therapy, and a variety of anticancer agents have been developed so far. Thus, many antitumor antibiotics and other antitumor agents, which directly act on tumor cells and produce a cytocidal effect on the cells, have been developed. However, these agents are also highly cytotoxic to normal cells or tissues, and severe side effects have been unavoidable in the majority of cases. Accordingly, the development of an antitumor agent which has selective cytotoxicity against tumor cells but shows few side effects has long been researcher's ambition.
Although tumor cells have not been fully characterized, it is considered that dormant oncogenes on chromosomes are expressed as a result of stimulation by carcinogenic chemicals, radiation, ultraviolet rays or carcinogenic viruses, or conversely, as a result of inactivation of tumor suppressor genes by such stimulation. It is believed that intra- and extra-cellular secretion of expression products of the oncogenes or their attachment to cell membranes is related to the acquisition of the neoplastic properties specific to tumor cells, such as metastasis, infiltration ability and uncontrolled proliferation. If any method to inhibit one of the processes caused by the abnormal expression becomes available, such a method is expected to provide an effective tool for controlling cancers.
In Japan, candidates for antitumor agents have been screened for their effectiveness according to the NCI (U.S. National Cancer Institute) antitumor drug screening protocol using mouse leukemia cell lines L1210 and P388. However, the results of the screening test have frequently been inconsistent with the corresponding therapeutic results in patients suffering from cancers. Recently modified new NCI screening protocol uses human cancer cell lines, and good correlation has been found between the results of the new test and therapeutic results in clinical studies [G. B. Grindey: Cancer Cells 2 (6): p.163-171, 1990; N. Saijo, Clinician 17 (6): p.4-9, 1991].
As the results of screening of a variety of compounds for their antitumor activities by means of the new NCI screening protocol using human cancer cell lines, the present inventors have found that 2-(1-hydroxyethyl)-5-hydroxynaphtho[2,3-b]furan-4,9-dione (referred to as NFD hereinafter), a novel compound extracted from Tabebuia avellanedae Lorentz, ex Griseb., which belongs to the family Bignoniaceae, has excellent antitumor activity. The present invention has been completed based on the findings.
Accordingly, an object of the present invention is to provide NFD, a novel compound having the following formula (1). ##STR2##
It is a further object of this invention to provide antitumor agents comprising NFD as an active ingredient.
It is yet another object of the present invention to provide the process for manufacturing NFD comprising the steps of: extracting the dried bark of Tabebuia avellanedae Lorentz, ex Griseb. with hot methanol; extracting a residue obtained by evaporation of the extract with cold chloroform; and separating chloroform-soluble components by preparative thin-layer chromatography using toluene/ethyl acetate (4:1) as a developing solvent system.
NFD (molecular formula: C.sub.14 H.sub.10 O.sub.5 ; molecular weight: 258.230) occurs as yellow needles with a melting point of 181.degree. C., which is freely soluble in dimethylsulfoxide and chloroform and slightly soluble in water.
NFD remarkably inhibits the growth of the following tumor cells at low concentrations and exhibits selective toxicity to these tumor cells: cultured human lung adenocarcinoma cell lines A-549, VMRC-LCD and SK-LU-1, human lung squamous cell carcinoma C
REFERENCES:
Ueda et al., Phyto Chemistry, vol. 36, No. 2, pp. 323-325 (1994).
Chemical Abstracts III:160194e (1989).
Wagner et al, Helvetica Chimica Acta, vol. 72, pp. 659-667 (1989).
Fujimoto et al., J. Chem. Soc. Perkin Trans. 1, pp. 22323-22327 (1991).
Hatanaka Heihachi
Hirai Keiichi
Tokuda Harukuni
Ueda Shinichi
Goldberg Jerome D.
Taheebo Japan Co., Ltd.
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