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ABSTRACT: Substituted isoquinolin-1-ones (1) were synthesized to test theirin vitro anticancer activity. 3-Biphenyl-N-methylisoquinolin-1-one (7) showed the most potent anticancer activity against five different human cancer cell lines.
Archives of Pharmacal Research 04/2012; 24(4):276-280. · 1.59 Impact Factor
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ABSTRACT: 5-Aryl-2,3-dihydroimidazo[2,1-a]isoquinolines were reported to have strong antitumor activity and one of the derivatives such as 5-[4′-(piperidinomethyl)phenyl]-2,3-dihydroimidazo[2,1-a] isoquinoline (1, SDZ 62–434) was found to be more effective than the clinical cytostatic agent edelfosine (2) inin vitro andin vivo assays. Currently SDZ 62–434 is in clinical trials in Europe. The structure-activity relationship studies of SDZ 62–434 showed
that compounds with substitution on ring A were less active than the lead compound. Ring B in SDZ 62–434 was essential for
the activity because compounds without B ring had no antitumor activity. Among the 3-arylisoquinolin-1-one derivatives, 3-[4′-(piperidonomethyl)phenyl]
substituted analog had no antitumor activity but simple phenyl substituted compound, such as4, showed the most potent antitumor activity in various human tumor cell lines.
Archives of Pharmacal Research 03/1997; 20(2):138-143. · 1.59 Impact Factor
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ABSTRACT: Doxorubicin, one of the clinically most useful anticancer agents, is used alone or in combination with other drugs against
a wide variety of tumors, recently. But cancer cells developed resistance to this agent in many ways. This resistance is an
important limiting factor of doxorubicin for anticancer drug. We newly established doxorubicin-resistant HCT15/CL02 subline
from parental HCT15 human adenocarcinoma colon cancer cells. HCT15/CL02 revealed resistance to doxorubicin about 85-fold of
its parental cells, and it also revealed cross-vealed to actinomycin D, etoposide and vinblastine but not to cisplatin and
tamoxifen. And verapamil, a reversal agent of multidrug-resistance (MDR) by P-glycoprotein, elevated the cytotoxicity of doxorubicin
against both HCT15 and HCT15/CL02 cells. But the relative resistant rate was not reduced. Verapamil had no effects on the
toxicity of cisplatin to the both cell lines. These results indicate that HCT15/CL02 cells have some functionally complex
mechanisms for MDR.
Archives of Pharmacal Research 09/1996; 19(5):342-347. · 1.59 Impact Factor
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ABSTRACT: Phenolic compounds are prevalent as toxins or environmental pollutants, but they are also widely used as drugs for various
purpose including anticancer agent. A novel biphenolic compound, bis(2-hydroxy-3-tert-butyl-5-methylphenyl)methane (GERI-BP002-A) was isolated from the fermentation broth ofAspergillus fumigatus F93 previously, and it has revealed cytotoxicity against human solid tumor cells. Its effective doses that cause 50% inhibition
of cell growthin vitro against non-small cell lung cancer cell A549, ovarian cancer cell SK-OV-3, skin cancer cell SK-MEL-2 and central nerve system
cancer cell XF498 were 8.24, 10.60, 8.83, 9.85 μg/ml respectively. GERI-BP002-A has also revealed cytotoxicity against P-glycoprotein-expressed
human colon cancer cell HCT15 and its multidrug-resistant subline HCT15/CL02, and its cytotoxicity was not affected by P-glycoprotein.
We have also tested cytotoxicities of structurally related compounds of GERI-BP002-A such as diphenylmethane, 1,1-bis(3,4-dimethylphenyl)ethane,
2,2-diphenylpropane, 2-benzylpyridine, 3-benzylpyridine, 4,4′-di-tert-butylphenyl, bibenzyl, 2,2′-dimethylbibenzyl,cis-stilbene,trans-stilbene, 3-tert-butyl-4-hydroxy-5-methylphenylsulfide, sulfadiazine and sulfisomidine for studying of structure and activity relationship,
and from these data we could suppose that hydroxyl group of GERI-BP002-A conducted important role in its cytotoxicity.
Archives of Pharmacal Research 04/1996; 19(4):286-291. · 1.59 Impact Factor
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ABSTRACT: The trichothecenes are sesquiterpenoid mycotoxins characterized by the 12,13-epoxytrichothec-9-ene ring system. We have tested
cytotoxicity of several naturally-occurring or synthesized trichothecenes against human solid tumor cell lines. Among them,
trichothecin (I) and 4-β-Acetoxy-12,13-epoxytrichothec-9-ene (trichodermin, II) exhibited highly cytotoxic activities. 4-β-Hydroxy-12,13-epoxytrichothec-9-ene
(trichodermol, III) and 4-β-Methoxy-12,13-epoxytrichothec-9-ene and 4-α-Hydroxy-12,13-epoxytrichothec-9-ene(VI) had no cytotoxicities
up to 10 μg/ml. And in the tested cell lines, HCT15 colon cancer cell line was the most sensitive to all tested trichothecenes.
Archives of Pharmacal Research 04/1996; 19(1):6-11. · 1.59 Impact Factor
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ABSTRACT: Aiming at the development of anticancer agents by modification of phenolic benzo[c]phenanthridine alkaloid, additional hydroxyl group was put on C10 position of fagaridine (1) by a biomimetic synthetic procedure to afford 10-hydroxyfagaridine (12). All of the synthetic intermediates were also screenedin vitro antitumor activities against five different cell lines as well as12. Among them the representative cytotoxic results are shown as follows;p-quinone (11) [ED50 (A549=0.22 μg/ml), (HCT15=0.21 μg/ml), fagaridine (1) (HCT 15=0.41 μg/ml), olefin (6) (HCT 15=0.06 μg/ml), acetal (7) (SKMEL-2=0.07 μg/ml), dihydrofagaridne (10) (A549=0. 38 μg/ml), 10-hydroxyfagaridine (12) (A 549=0.45 μg/ml). From these observation three main remarks can be drawn; (i) the iminium part of benzo[c]phenanthridine is not essential for showing acitvities, (ii) the additional hydroxyl group did not contribute to enhance
the cytotoxicity, (iii) the 3-arylisoquinolin-1(2H)-one derivatives were found to display significantin vitro antitumor activity.
Archives of Pharmacal Research 04/1996; 19(4):321-325. · 1.59 Impact Factor
