WO2001051004A2 - Anti-cancer agent containing naphthoquinone compound - Google Patents

Anti-cancer agent containing naphthoquinone compound Download PDF

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Publication number
WO2001051004A2
WO2001051004A2 PCT/KR2001/000026 KR0100026W WO0151004A2 WO 2001051004 A2 WO2001051004 A2 WO 2001051004A2 KR 0100026 W KR0100026 W KR 0100026W WO 0151004 A2 WO0151004 A2 WO 0151004A2
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WO
WIPO (PCT)
Prior art keywords
carbons
hydroxy
hydrogen
alkyl
alkoxy
Prior art date
Application number
PCT/KR2001/000026
Other languages
English (en)
French (fr)
Other versions
WO2001051004A3 (en
Inventor
Hee-Yong Han
Young-Bum Kim
Jeong-Soo Kim
Ho-Jin Park
Moon-Jong Noh
Original Assignee
Kolon Industries, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kolon Industries, Inc. filed Critical Kolon Industries, Inc.
Publication of WO2001051004A2 publication Critical patent/WO2001051004A2/en
Publication of WO2001051004A3 publication Critical patent/WO2001051004A3/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 

Definitions

  • the present invention relates to an anti-cancer drug containing
  • naphthoquinone compound and more particularly, to an anti-cancer drug containing naphthoquinone compounds of formula 1 and formula 2 that have low toxicity and excellent anti-cancer activity.
  • R is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons;
  • R 2 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl from having from 1 to 10 carbons, ester having from 1 to 10 carbons, or
  • alkene having from 1 to 10 carbons
  • R 3 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 4 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 5 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons.
  • R is hydrogen, hydroxy, primary amine, secondary amine, tertiary amine, carboxylic acid, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1
  • R 2 is hydrogen, hydroxy, primary amine, secondary amine, tertiary amine, carboxylic acid, alkoxy having from 1 to 10 carbons, alkyl having from
  • R 3 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 4 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 5 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons.
  • tumors are either malignant or benign.
  • Malignant tumors are disease that the present medicine overcomes. The occurrence of cancer is increasing every year and it is reported that cancer is the cause of a high percentage of deaths in Korea.
  • the currently developed anti-cancer drugs have several side effects due to their toxicity to both cancerous cells and normal cells, and are not effective due to the existence of drug-resistant cells.
  • the present invention provides an
  • anti-cancer drug including naphthoquinone compounds of formula 1.
  • R is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 2 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 3 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene
  • R 4 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene
  • R 5 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons.
  • the present invention provides an anti-cancer drug including
  • R is hydrogen, hydroxy, primary amine, secondary amine, tertiary
  • amine carboxylic acid, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1
  • R 2 is hydrogen, hydroxy, primary amine, secondary amine, tertiary
  • ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons;
  • R 3 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl
  • R 4 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons;
  • R 5 is hydrogen, hydroxy, alkoxy having from 1 to 10 carbons, alkyl having from 1 to 10 carbons, ester having from 1 to 10 carbons, or alkene having from 1 to 10 carbons.
  • naphthoquinone compounds of formula 1 and formula 2 have low toxicity
  • the present invention contains naphthoquinone compound of
  • invention contains a pharmaceutically acceptable nontoxic salt based on
  • naphthoquinone compound of formula 1 and formula 2 solvent and isomer.
  • the naphthoquinone compound is compound of formula 1.
  • R is hydrogen or hydroxy
  • R 2 is hydrogen or alkyl having from 1 to 5 carbons
  • R 3 is hydrogen or hydroxy
  • R 4 is hydrogen, hydroxy, alkene having from 1 to 5 carbons, alkoxy
  • R 5 is hydrogen, hydroxy, alkyl having from 1 to 5 carbons, or alkoxy
  • the naphthoquinone compound is compound of
  • R is hydrogen or hydroxy
  • R 2 is methyl
  • R 3 is hydrogen
  • R 4 is alkyl having from 1 to 5 carbons, ester having from 1 to 5
  • R 5 is alkyl having from 1 to 5 carbons. In addition, it prefers naphthoquinone compound of formula 2;
  • R is hydrogen, hydroxy, primary amine, secondary amine, tertiary
  • amine carboxylic acid, alkoxy having from 1 to 5 carbons, alkyl having from 1 to 5 carbons, ester having from 1 to 5 carbons, or alkene having from 1 to
  • R 2 is hydrogen, hydroxy, primary amine, secondary amine, tertiary
  • amine carboxylic acid, alkoxy having from 1 to 5 carbons, alkyl having from 1 to 5 carbons, ester having from 1 to 5 carbons, or alkene having from 1 to 5 carbons;
  • R 3 is hydrogen or hydroxy
  • R 4 is hydrogen, hydroxy, alkyl having from 1 to 5 carbons, or alkoxy
  • R 5 is hydrogen, hydroxy, alkyl having from 1 to 5 carbons, or alkoxy having from 1 to 5 carbons.
  • the anti-cancer drug including the
  • naphthoquinone compound can be prepared as an applicable type when the drugs contain derivatives of formula 1 or formula 2.
  • the anti-oxidation of formula 1 or formula 2 the anti-oxidation of formula 1 or formula 2.
  • cancer drug of the present invention can be formulated as a tablet, a capsule,
  • the anti-cancer drug including the
  • naphthoquinone compound preferably contains 0.01 % to 50 wt% of the naphthoquinone compound of the formula 1 or the formula 2 and more
  • the anti-cancer drug of the present invention has low toxicity
  • naphthoquinone compound includes naphthoquinone compound as an active principle and can be applied as any type.
  • the anti- cancer drug can be formulated as a tablet, a capsule, as a solution, in granulated form, or in a solid type, and can be applied orally, by injection, or local ointment.
  • Table 1 below represents a manufacturing example of solution type.
  • the manufacturing method comprised the mixing step of the ingredients of
  • the unit is wt%.
  • Table 2 below is the manufacturing example of a tablet.
  • the unit is wt%.
  • the human cancer cells used for the test were A549 (lung
  • HCT15 cancer of the colon
  • SK-OV-3 ovary cancer
  • SK-OV-3 ovary cancer
  • MEL-2 (cutaneous cancer).
  • the cancer cell was incubated at 37 ° C in 5 % of CO 2 incubator.
  • Used media was a basic media, RPMI and 10 % FBS was added to the media.
  • test cell toxicity the cancer cell in exponential phase were
  • LD 50 lethal dose 50 % of laboratory animals
  • the naphthoquinone compound is very safe to the human body.
  • the naphthoquinone compound is very toxic to the human cancer cell but is safe to the human body.
  • the anti-cancer drug is very toxic to the human cancer cell but is safe to the human body.
  • naphthoquinone compound of the present invention has little toxicity and remarkable anti-cancer activity, and it is expected that the anti- cancer drug will play an important part in the treatment of cancer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
PCT/KR2001/000026 2000-01-10 2001-01-09 Anti-cancer agent containing naphthoquinone compound WO2001051004A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20000000954 2000-01-10
KR2000/954 2000-01-10
KR10-2000-0085805A KR100406736B1 (ko) 2000-01-10 2000-12-29 나프토퀴논계 화합물을 포함하는 항암제
KR2000/85805 2000-12-29

Publications (2)

Publication Number Publication Date
WO2001051004A2 true WO2001051004A2 (en) 2001-07-19
WO2001051004A3 WO2001051004A3 (en) 2002-01-17

Family

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KR (1) KR100406736B1 (ko)
WO (1) WO2001051004A2 (ko)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100406736B1 (ko) * 2000-01-10 2003-11-21 주식회사 코오롱 나프토퀴논계 화합물을 포함하는 항암제
CN1318414C (zh) * 2004-12-30 2007-05-30 中山大学 含邻萘醌结构的化合物及其应用
CN100413867C (zh) * 2002-11-12 2008-08-27 诺瓦提斯公司 4-氨基-5-苯基-7-环己基-吡咯并[2,3-d]嘧啶衍生物
CN102125545A (zh) * 2010-12-07 2011-07-20 中山大学 含邻醌结构的化合物在制备抗肿瘤药物中的应用
CN102716116A (zh) * 2010-12-07 2012-10-10 中山大学 含邻醌结构的化合物在制备抗肿瘤药物中的应用
CN103183668A (zh) * 2013-02-19 2013-07-03 中山大学 一种天然产物曼宋酮e的衍生物及其制备与应用
CN104744421A (zh) * 2015-01-08 2015-07-01 中山大学 一种Mansonone F的衍生物及其制备方法和应用

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100455458B1 (ko) * 2001-10-18 2004-11-08 (주)바이오니아 1,2-나프토퀴논유도체 및 약학적으로 허용되는 이들의염과 그 제조방법
KR101990054B1 (ko) * 2017-04-25 2019-06-17 대구대학교 산학협력단 로손을 유효성분으로 포함하는 항암 조성물

Citations (1)

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KR19980067139A (ko) * 1997-01-31 1998-10-15 서영거 만소논에프를 주성분으로 하는 항균제

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JPS63270673A (ja) * 1987-04-30 1988-11-08 Nobuo Ikegawa 制癌剤とその製造方法
KR100406736B1 (ko) * 2000-01-10 2003-11-21 주식회사 코오롱 나프토퀴논계 화합물을 포함하는 항암제
KR100462844B1 (ko) * 2000-12-06 2004-12-20 한국생명공학연구원 느릅나무과로부터 분리한 신규한 화합물 및 그 제조방법

Patent Citations (1)

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KR19980067139A (ko) * 1997-01-31 1998-10-15 서영거 만소논에프를 주성분으로 하는 항균제

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEN C.M. ET AL.: 'Constituents of formosan antitumor folk medicine. Part 3. A mansonone from helicteres angustifolia' PHYTOCHEMISTRY vol. 29, no. 3, 1990, pages 980 - 982 *
FERNANDEZ ET AL.: 'Redox cycling of o-naphtoquinones in trypanosomatids. Superoxide and hydrogen peroxide production' BIOCHEM. PHARMACOL. vol. 52, no. 12, 1996, pages 1875 - 1882 *
INBARAJ ET AL.: 'Cytotoxicity and superoxide anion generation by some naturally occurring quinones' FREE RADICAL BIOL. MED. vol. 26, no. 9/10, 1999, pages 1072 - 1078 *
KIM J.P. ET AL.: 'Isolation and identification of sesquiterpene o-naphtoquinones, mansonones E,F and H, from the root bark of Ulmus davidiana planch' HAN'GUK NONGHWA HAKHOECHI vol. 39, no. 1, 1996, pages 89 - 94 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100406736B1 (ko) * 2000-01-10 2003-11-21 주식회사 코오롱 나프토퀴논계 화합물을 포함하는 항암제
CN100413867C (zh) * 2002-11-12 2008-08-27 诺瓦提斯公司 4-氨基-5-苯基-7-环己基-吡咯并[2,3-d]嘧啶衍生物
CN1318414C (zh) * 2004-12-30 2007-05-30 中山大学 含邻萘醌结构的化合物及其应用
CN102125545A (zh) * 2010-12-07 2011-07-20 中山大学 含邻醌结构的化合物在制备抗肿瘤药物中的应用
CN102716116A (zh) * 2010-12-07 2012-10-10 中山大学 含邻醌结构的化合物在制备抗肿瘤药物中的应用
CN102716116B (zh) * 2010-12-07 2013-11-06 中山大学 含邻醌结构的化合物在制备抗肿瘤药物中的应用
CN103183668A (zh) * 2013-02-19 2013-07-03 中山大学 一种天然产物曼宋酮e的衍生物及其制备与应用
CN104744421A (zh) * 2015-01-08 2015-07-01 中山大学 一种Mansonone F的衍生物及其制备方法和应用

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Publication number Publication date
KR20010070381A (ko) 2001-07-25
KR100406736B1 (ko) 2003-11-21
WO2001051004A3 (en) 2002-01-17

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