• Title/Summary/Keyword: Antitumor compounds

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Studies on the synthesis of N,N'-disubstituted thiourea derivatives and their antibacterial, antitubercular and antitumor activities (N,N'-diusbstituted thiourea derivatives의 합성과 항균성, 항인결핵성및 항종양 시험에 관한 연구)

  • 조윤성;이명걸
    • YAKHAK HOEJI
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    • v.14 no.1_2
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    • pp.1-14
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    • 1970
  • Seventeen N,N/sup I/-disubstituted thiourea derivatives were synthesized by the Hugershof reaction and reported. Antitumor activities of the synthesized compounds against ascitic Ehrlich Carcinoma and ascitic sarcoma 180 were reported. It was found that 1,1/sup I/-(p-Phenylene)-3,3/sup I/-bis (2-carboxyphenyl)-2,2/sup I/-dithiourea was considerably active against ascitic Ehrlich Carcinoma and Sarcoma 180 respectively. 1-(2-Carboxyphenyl)-3-(p-ethoxyphenyl)-2 thiourea was active against ascitic Sarcoma 180. 1-Salicyloyl-3-(p-ethoxyphenyl)-2-thiourea and 1,1/sup I/-(p-Phenylene)-3,3/sup I/-bis(2-hydroxyethyl)-2,2/sup I/-dithiourea were active against ascitic Ehrlich Carcinoma. Antitubercular activities of the synthesized compounds against Mycobacterium tuberculosis H/sub 37/ R/sub v/ were also reported. It was found that 1-Isonicotinyl-4-cyclohexyl-3-thiosemicarbazide was considerably active at 100 .mu.g/ml. 1,1/sup I/-(p-Phenylene)-3,3/sup I/-bis(2-hydroxyethyl)-2,2/sup I/-dithiourea and 1-Salicyloyl-3-(p-ethoxyphenyl)-2-thiourea were active at 1000 .mu.g/ml respectively. Antibacterial activities of nine compounds of the synthesized compounds against S. aureus and E. Coli were reported. It was found that 1,1-(p-Phenylene)-4,4/sup I/-bis(isonicotinyl)-2,2/sup I/-dithiosemicarbazide and 1-Isonicotinyl-4-cyclohexyl-3-thiosemicarbazide were considerably active against S. aureus and E. Coli respectively. 1-(6-Methyl-2-benzothiazolyl)-3-(1-naphthyl)-2-thiourea was active against S. aureus. 1,1/sup I/-(p-Phenylene)-3,3/sup I/-bis (2-hydroxyethyl)-2,2/sup I/-dithiourea was active against E. Coli.

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Synthesis of 6-Aziridinylbenzimidazole Derivatives and Their In Vitro Antitumor Activities

  • Ahn, Chan-Mug;Kim, Soo-Kie;Han, Jeong-Lim
    • Archives of Pharmacal Research
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    • v.21 no.5
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    • pp.599-609
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    • 1998
  • In search for new antitumor agents, twelve 6-aziridinylbenzimidazole derivatives were synthesized and their cytotoxicities were tested against three cancer cell lines (mouse lymphocytic leukemia P388 and B16, and human gastric carcinoma SNU-16). From 4-amino-3-nitrotoluene as the starting material, 2-(acetoxymethyl)benzimidazoles (5a-d) were obtained by Phillips reaction. These benzimidazoles were then reacted with Fremy's salt to give a mixture of three 2-(acetoxymethyl) (8a-c) and four 2-(hydroxymethyl)benzimidazole-4,7-diones (9a-d). Addition of these quinones with aziridine afforded 6-aziridinyl-2-(acetoxymethyl) (10a-c) and 6-aziridinyl-2-(hydroxymethyl)benzimidazole-4,7-diones (11a-d). Utilizing 2-(hydroxymethyl)benzimidazole-4,7-diones (9b,d), esters 10d and 13e-h were prepared by the sequential reactions of esterification and addition. The synthesized compounds show potent cytotoxicity against all of three cell lines tested. The cytotoxicities of 10a-d or 11a-d against SNU-16 were wuperior to those of 13e-h, and were equal to or slightly higher than that of mitomycin C. compounds 11a-d were slightly more cytotoxic than 10a-d in all cell lines tested.

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Synthesis and Biological Activity of Geranyloxy Compounds

  • Oh, Hyun-Ju;Oh, In-Kio;Na, Young-Soon;Kim, Myung-Ju;Baek, Seung-Hwa
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.3
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    • pp.792-796
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    • 2005
  • Disk assays on the compounds (10 and 12) showed both to have antifungal activity against the dermatophytic fungus Trichophyton mentagrophytes ATCC 28185, (1 and 3 mm inhibition zones at $60\;{\mu}g/disc$), but not against the Gram-positive bacterium B. subtilis or the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa or fungi Cladosporium resinae and Candida albicans. However, the compound (13) did not show against antifungal activity. The geranyloxy compounds (10, 12, and 13) were cytotoxic to P388 murine leukaemia cells ATCC CCL 46 P388D1, ($IC_50$ >6,250 ng/mL at $7.5\;{\mu}g/disc$). These results suggest that The geranyloxy compounds possesses antimicrobial and antitumor activities.

Synthesis and evaluation of antimicrobial-antitumor activities of methylthiosemi-carbazones and thiocarbohydrazones

  • Rhee, Shang-Hi
    • YAKHAK HOEJI
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    • v.16 no.4
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    • pp.162-175
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    • 1972
  • Fifty six compounds of 4-methylthiosemicarbazone and thiorcarbohydrazone derivatives were prepared and subjected to biological tests. The following five compounds, 2-hydroxybenzaldehyde monothiocarbohydrazone (2),4-methylbenzaldehyde monothiocarbohydrazone (8), 1-(2-hydroxybenzaldehyde)-5(4-hydroxy-3-methoxybenzaldehyde) dithiocarbohydrazone (45), 1-(2-hydroxybenzaldehyde)-5-furfural dithiocarbohydrazone (46) and 1-benzaldehyde-5-cinnamaldehyde dithiocarbohydrazone (49) exhibited marked antimicrobial activity against E. coli, St. aureus and P. chrysogenum. In addition to these compounds, 3-methoxybenzaldehyde monothiocarbohydrazone (12) and 4-methylbenzaldehyde dithiocarbohydrazone (29) showed marked inhibition of HeLa cell growth at the concentration of 10 ${\nu}$g/ml. It was generally observed that most compounds demonstrated significant antifungal activity against P. chrysongenum but only one compound, 3-hydroxy-4-methoxybenzaldehyde dithiocarbohydrazone (39), exerted antituberculosis activity against M. tuberculosis H$_{37}$ RV at the concentration of 10 ${\nu}$g/ml.

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Synthesis of Coumarin Analogues and their Antitumor Activity (쿠마린 유도체의 합성과 그들의 항암효과)

  • Lee, Jee-Hyun;Lee, Jae-Ho;Kim, Hyun-Kwan;Kim, Eui-Geom;Shen, Gui-nan;Cho, Soo-Hyun;Myung, Chang-Seon;Kim, Dong-Hee;Yun, Mi-Young;Choi, Yong-Seok;Kim, Sung-Hoon;Song, Gyu-Yong
    • YAKHAK HOEJI
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    • v.50 no.5
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    • pp.338-344
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    • 2006
  • A novel series of 4-senecioyloxymethyl-6,7-dimethoxycoumarin, isolated from Crinum latifolium, was prepared by reacting 4-bromomethyl or 4-bromomethyl-6,7- dimethoxycoumarin with various carboxylic acids and examined for their anti-angiogenic activities in human umbilical vein endothelial cells (HUVECs). Among them, 4e, 4f, 4g and 4i with noncyclic moiety exhibited potent anti-angiogenic activity. However, compounds with cyclic moiety such as phenyl, pyridinyl, thiophenyl and furanyl group did not exhibit any anti-angiogenic activity. Also, compounds 4f and 4g which exhibited strong anti-angiogenic activity in a dose-dependent manner showed antitumor activity.

Synthesis and Evaluation of Antitumor Activity of 2- and 6-[(1,3- Benzothiazol-2-yl)aminomethyl]-5,8-dimethoxy-1,4-naphthoquinone Derivatives

  • Chung, Yong-Seog;Shin, Young-Kook;Zhan, Chang-Guo;Lee, Sung-Duck;Cho, Hoon
    • Archives of Pharmacal Research
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    • v.27 no.9
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    • pp.893-900
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    • 2004
  • 2- or 6-Substituted BZT-N derivatives were synthesized, and their cytotoxic activity against can-cer L1210 and SNU-1 cells was examined. The antitumor action was also assessed in mice bearing S-180 cells in peritoneal cavity. In a comparison, it was found that 6-substituted BZT-N derivatives exhibited higher potencies in both bioactivities than 2-substituted BZT-N derivatives against L1210 cells in in vitro and S-180 in vitro tests exception of compound 36. Interestingly, it was observed that 2-substituted compound 36, which has methyl group at RI position, exhib-ited a better antitumor activity than 6-substituted compounds against L1210 and SNU-1 in vitro. The EDso value of 2-substituted compound 36 against L1210 was found to be comparable to the EDso value of adriamycin and was even better against the solid cancer cell line SNU-1. It was also observed that 2-substituted compound 36 showed better antitumor activity in mice bearing S-180 cells in the peritoneal cavity. The T/C (%) value of 2-substituted compound 36 was simi-lar to that of adriamycin. Quantitative structure-activity relationship (QSAR) tests reveal that the experimental E $D_{50}$ values against SNU-1 closely correlate with both the calculated HOMO ener-gies ( $E_{HOMO}$) and the measured H-NMR chemical shift of 3-H ($\delta$$_{H}$). The results suggests that a compound having higher $E_{HOMO}$ and $\delta$$_{H}$ values usually should have a lower E $D_{50}$ (SNU-1) value.lue.lue.lue.

In vitro and In vivo Antitumor Activity of Tiliacorinine in Human Cholangiocarcinoma

  • Janeklang, Somkid;Nakaew, Archawin;Vaeteewoottacharn, Kulthida;Seubwai, Wunchana;Boonsiri, Patcharee;Kismali, Gorkem;Suksamrarn, Apichart;Okada, Seiji;Wongkham, Sopit
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.17
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    • pp.7473-7478
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    • 2014
  • Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with $IC_{50}$ $4.5-7{\mu}M$ by inducing apoptosis through caspase activation, upregulation of BAX, and downregulation of $Bcl_{xL}$ and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.

Antitumor Activity of Cell Suspension Culture of Green Tea Seed (Camellia sinensis L.)

  • Choi, Jae-Hoon;Yoon, Sang-Kun;Lee, Keyong-Ho;Seo, Min-Soo;Kim, Doo-Hwan;Hong, Seung-Beom;Kim, Ji-Yeon;Paik, Hyun-Dong;Kim, Chang-Han
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.11 no.5
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    • pp.396-401
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    • 2006
  • The objective of this study was to investigate the antitumor activity of suspension cultures of tea callus cells grown in the presence of different concentrations of the growth regulator 2,4-dichlorophenoxy acetic acid (2,4-D) with or without light irradiation. The methanol and ethanol extracts of precipitated cells (MEP, EEP) exhibited stronger inhibitory effects on the growth of tumor cell lines than the water extract of precipitated cells (WEP) or the supernatant Compared to culture under dark conditions, exposure to light irradiation led to significantly higher antitumor activity. The MEP from light irradiated cells at $250{\mu}g/mL$ with 2.0mg/L 2,4-D displayed more than 64% growth inhibition of HEP-2 cells, whereas normal cells showed less than 25% growth inhibition. The some fractions of MEP obtained from Diaion HP-20 column chromatography displayed the majority of inhibitory activity against the HEP-2 cell line. These results show that 2,4-D, and light stimulated the synthesis of antitumor compounds.

Potential Antitumor ${\alpha}$-methylene-${\gamma}$-butyrolactone-bearing nucleic acid bases. 2. synthesis of $5^I-Methyl-5^I$-[2-(5-substituted uracil-1-yl)ethyl]-$2^I-oxo-3^I$-methylenetetrahydrofurans

  • Kim, Jack-C.;Kim, Ji-A;Park, Jin-Il;Kim, Si-Hwan;Kim, Seon-Hee;Choi, Soon-Kyu;Park, Won-Woo
    • Archives of Pharmacal Research
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    • v.20 no.3
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    • pp.253-258
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    • 1997
  • Ten, heretofore unreported, $ 5^I-methyl-5^I-[2-(5-substituted uracil-1-yl)ethyl)]-2^I-oxo-3^I$-methylenetetrahydrofurans (H, F, Cl, Br, I, $ CH_3$,$CF_3$,$CH_2CH_3$,$ CH=CH2$, SePh) (7a-j) were synthesized and evaluated against four cell lines (K-562, FM-3A, P-388 and U-937). For the preparation of ${\alpha}$-methylene-${\gamma}$-butyrolactone-linked to 5-substituted uracils (7a-j), the convenient Reformasky type reaction was employed which involves the treatment of ethyl ${\alpha}$-(bromomethyl)acrylate and zinc with the respective 1-(5-substituted uracil-1-yl)-3-butanone (6a-j). The 5-substituted uracil ketones (6a-j) were directly obtained by the respective Michael type reaction of vinyl methyl ketone with the $K_2CO_3$(or NaH)-treated 5-substituted uracils (5a-j) in the presence of acetic acid in the DMF solvent. The .alpha.-methylene-.gamma.-butyrolactone compounds showing the most significant antitumor activity are 7e, 7f, 7h and 7j (inhibitory concentration $(IC_50)$ ranging from 0.69 to $2.9 {\mu}g/ml$), while 7b, 7g and 7i have shown moderate to significant activity. The compounds 7a, 7c and 7d were found to be inactive. The synthetic intermediate compounds 6a-j were also screened and found marginal to moderate activity where compounds 6b and 6g showed significant activity $(IC_50:0.4~2.8 {\mu}g/ml)$.

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Biotoxins for Cancer Therapy

  • Liu, Cui-Cui;Yang, Hao;Zhang, Ling-Ling;Zhang, Qian;Chen, Bo;Wang, Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4753-4758
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    • 2014
  • In recent times, a number of studies have provided evidence that biotoxins present great potential as antitumor agents, such as snake venom, bee venom, some bacteria toxins and plant toxins, and thus could be used as chemotherapeutic agents against tumors. The biodiversity of venoms and toxins make them a unique source from which novel anticancer agent may be developed. Biotoxins, also known as natural toxins, include toxic substances produced by plants, animals and microorganisms. Here, we systematically list representative biological toxins that have antitumor properties, involving animal toxins, plant toxins, mycotoxins as well as bacterial toxins. In this review, we summarize the current knowledge involving biotoxins and the active compounds that have anti-cancer activity to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. We also show insights into the molecular and functional evolution of biotoxins.