8-Quinolinamines and their pro prodrug conjugates as potent blood-schizontocidal antimalarial agents

Bioorganic and Medicinal Chemistry

Volumn 11, Issue 21, 2003, Pages 4557-4568

  Vangapandu, Suryanarayana ^a,b   Sachdeva, Sandeep ^a   Jain, Meenakshi ^a   Singh, Savita ^a   Singh, Prati Pal ^a   Kaul, Chaman Lal ^a   Jain, Rahul ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

^b UNIVERSITY OF MISSISSIPPI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 [2 [4 (4 ETHYL 5 HEPTOXY 6 METHOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; 2 [2 [4 (4 ETHYL 5 HEXOXY 6 METHOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; 2 [2 [4 (4 ETHYL 6 METHOXY 5 OCTOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; 2 [2 [4 (4 ETHYL 6 METHOXY 5 PENTOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; 2 [2 [4 (4 ETHYL 6 METHOXY 5 PROPOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; 2 [2 [4 (5 BUTOXY 4 ETHYL 6 METHOXY 8 QUINOLYLAMINO)PENTACARBAMOYL] 1,1 DIMETHYLETHYL] 3,5 DIMETHYLPHENYLACETATE; AMIDE; ANTIMALARIAL AGENT; CHLOROQUINE; ESTERASE; N 1 [4 (4 ETHYL 5 HEPTOXY 6 METHOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 1 [4 (4 ETHYL 5 HEXOXY 6 METHOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 1 [4 (4 ETHYL 6 METHOXY 5 OCTOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 1 [4 (4 ETHYL 6 METHOXY 5 PENTOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 1 [4 (4 ETHYL 6 METHOXY 5 PROPOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 1 [4 (5 BUTOXY 4 ETHYL 6 METHOXY 8 QUINOLYLAMINO)PENTYL] 3 (2,4 DIMETHYL 3,6 DIOXO 1,4 CYCLOHEXADIENYL) 3 METHYLBUTANAMIDE; N 8 (4 AMINO 1 METHYLBUTYL) 4 ETHYL 5 HEPTOXY 6 METHOXY 8 QUINOLINAMINE; N 8 (4 AMINO 1 METHYLBUTYL) 4 ETHYL 5 HEXOXY 6 METHOXY 8 QUINOLINAMINE; N 8 (4 AMINO 1 METHYLBUTYL) 4 ETHYL 6 METHOXY 5 OCTOXY 8 QUINOLINAMINE; N 8 (4 AMINO 1 METHYLBUTYL) 4 ETHYL 6 METHOXY 5 PENTOXY 8 QUINOLINAMINE; N 8 (4 AMINO 1 METHYLBUTYL) 4 ETHYL 6 METHOXY 5 PROPOXY 8 QUINOLINAMINE; N 8 (4 AMINO 1 METHYLBUTYL) 5 BUTOXY 4 ETHYL 6 METHOXY 8 QUINOLINAMINE; PRODRUG; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; COVALENT BOND; DRUG CONJUGATION; DRUG EFFICACY; DRUG SCREENING; DRUG SENSITIVITY; DRUG SYNTHESIS; FEMALE; MALARIA; MALE; MOUSE; NONHUMAN; OXIDATION REDUCTION REACTION; PLASMODIUM MALARIAE;

EID: 0141504172     PISSN: 09680896     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmc.2003.07.003     Document Type: Article

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40. 50 of the test compounds was then calculated.
41. 7 infected-erythrocytes from a donor mouse. Four hours later, mice were administered test compounds/chloroquine/vehicle, orally. A total of four doses were given orally on days D '0', D+1, D+2, and D+3. The tail blood smears were made on day D+4 and D+7, stained with Giemsa and examined microscopically. The minimum dose that completely suppressed parasitaemia on days D+4 and D+7 was termed as minimum effective dose (MED), and the minimum dose that cleared the parasitaemia for up to 60 days was termed as curative dose (CD). The terms 'curative', 'active' and 'inactive' are used to describe the biological activities exhibited by the tested compounds. The term 'curative' indicates complete elimination of malaria parasites from the body, so that relapse cannot occur up to day D+60. The term 'active' indicates that the treated animals show negative parasitaemia up to D+7. However, by D+28, some mice show negative and some mice may show positive test result for parasitaemia. The term 'inactive' indicates that the treated animals show positive test result for parasitaemia either on D+4 or D+7 or on both D+4 and D+7. The standard drug chloroquine has the MED of 8 mg/kg/day×4 (oral) and curative dose for the drug is 12 mg/kg/day×4 (oral) against P. berghei infected mice. On the other hand, chloroquine is found be ineffective against P. yoelii nigeriensis infection in mice up to the tested dose of 156 mg/kg/day×4 (oral).