Potential Antimalarials. XII. 4-Chloro-3-(substituted amino)methyl-5-[7-bromo (and 7-trifluoromethyl)-1,5-naphthyridin-4-ylamino]biphenyl-2-ols and 4-Chloro-3-(substituted amino)methyl-5-(7-trifluoromethyl-quinazolin-4-ylamino)biphenyl-2-ols

1990 ◽  
Vol 43 (8) ◽  
pp. 1367 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Sensitive Isolate

The mono- Mannich bases 3-(t- butylamino )methyl-4?-chloro-, 3-(4- benzylpiperidin-1-yl)methyl-4′-chloro-, 3-(4-benzylpiperazin-1- yl )methyl-4′-chloro-, 4′-chloro-3-diethylaminomethyl-, 4′-chloro-3-(pyrrolidin-1-yl)methyl-, 4′-chloro-3-(piperidin-1-yl)methyl- and 4′-chloro-3-(3- and 4- methylpiperidin-1-yl)methyl-5-[7-bromo (and 7- trifluoromethyl )-1,5-naphthyridin-4-ylamino]- biphenyl-2-ol, and the corresponding substituted 5-(7-trifluoromethylquinazolin-4-ylamino)bi- phenyl-2-ols, have been prepared by condensation of the 5-amino-3-(N- substituted aminomethyl )-4′-chlorobiphenyl-2-ols and the appropriate 4-chloro heterocycle. The antimalarial activity of these products against the chloroquine-sensitive isolate (FCQ-27) of Plasmodium falciparum revealed that the 1,5-naphthyridines reported here were less active than the corresponding di-Mannich bases, e.g. (6), derived from 4-[7- bromo (and 7-trifluoromethyl)-1?,5′-naphthyridin-4′-ylamino]phenol, a feature not shared by the corresponding quinazolines.

Potential Antimalarials. XVI. 4'-Chloro-3-[7″-chloro(and trifluoromethyl)quinolin-4″-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-Bromo(and 3'-trifluoromethyl)-3-(substituted amino)methyl-5-(7″-trifluoromethylquinolin-4″-yl)aminobiphenyl-2-ols

1992 ◽  
Vol 45 (11) ◽  
pp. 1845 ◽  
Author(s):  
GB Barlin ◽  
FL Tian ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
In Vitro Tests ◽  
Ic50 Values

Twenty-four mono-Mannich bases of the general formulae 4'-chloro-3-[7″-chloro(and trifluoro-methyl)quinolin-4'-yl]amino-5-(substituted amino)methylbiphenyl-4-ols and 4'-bromo(and 3'- trifluoromethyl-3(substituted amino)methyl-5(7″-trifluoromethylquinolin-4″-yl) aminobiphenyl-2-ols have been prepared by condensation of the 4-chloro heterocycle with 5-amino-3-(N-substituted amino)methyl-4'-chlorobiphenyl-4-ols or 5-amino-3-(N-substituted amino)methyl- 4'-bromo(or 3'-trifluoromethyl)biphenyl-2-ols. The antimalarial activity of these products in in vitro tests against Plasmodium falciparum reveals many with IC50 values of 50-100 nM ( chloroquine 20-40 nM ). The biphenyl-2-ols were more active than comparable biphenyl-4-ols.

Potential Antimalarials. IX. Di-mannich Bases of 4-(7′-trifluoro-methylquinazolin-4′-ylamino)phenol and 4-(7′-Trifluoromethylquinolin-4′-ylamino)phenol

1990 ◽  
Vol 43 (2) ◽  
pp. 311 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases

Syntheses are reported for a series of di-Mannich bases of 4-(7′-trifluoromethylquinazolin-4′-ylamino)phenol derived from 4-chloro-7-trifluoromethylquinazoline with the di-Mannich bases of 4-aminophenol. Some analogous quinolines were prepared similarly. When tested for antimalarial activity against Plasmodium falciparum in vitro, the quinazolines were rather less active than the corresponding quinolines.

Potential Antimalarials. VIII. Mono- and Di-mannich Bases of 2-(7′-Trifluoro-methylquinolin-4′-ylamino)phenol Via 2-Nitrophenols

1989 ◽  
Vol 42 (12) ◽  
pp. 2191 ◽  
Author(s):  
GB Barlin ◽  
JH Yan
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Bases ◽  
Nitro Compounds ◽  
Resistant Isolate ◽  
Sensitive Isolate

Di-Mannich bases have been prepared by the reaction of 2-nitrophenol and formaldehyde with dimethylamine, diethylamine, dipropylamine, pyrrolidine, piperidine, 2-, 3- and 4-methylpiperidine, 3,5-dimethylpiperidine and morpholine. The nitro compounds were reduced catalytically to the corresponding 2-aminophenols which with 4-chloro-7-trifluoromethylquinoline gave the di-Mannich bases of 2-(7′-trifluoromethylquinolin-4′-ylamino)phenol. Analogous compounds were synthesized from 3-and 5-methyl-2-nitrophenols, and pyrrolidine. The mono-Mannich compounds, 6-(3′-methylpiperidin-1′-ylmethyl)- and 6-(pyrrolidin-1′- ylmethyl)-2-(7″-trifluoromethylquinolin-4″-ylamino)pheno, were also prepared. The results for tests against a chloroquine-sensitive isolate (FCQ-27) and chloroquine-resistant isolate (K-1) of Plasmodium falciparum are reported.

Potential Antimalarials. XVII. Di- and Mono-Mannich Bases of 2(and 4)-[2(and 8)-Trifluoromethylquinolin-4-ylamino]phenol

1993 ◽  
Vol 46 (1) ◽  
pp. 21 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Sensitive Strain ◽  
In Vitro Tests ◽  
Derivatives Of

Di- and mono-Mannich base derivatives of 2(and 4)-[2(and 8)-trifluoromethylquinolin-4-ylamino]phenols have been prepared for comparison with the 7-trifluoromethyl isomers in tests for antimalarial activity. The order of activity in in vitro tests against the FC-27 ( chloroquine -sensitive) strain of Plasmodium falciparum was 7-CF3 >> 8-CF3 > 2-CF3.

Potential Antimalarials. XVIII. Some Mono- and Di-Mannich Bases of 3-[7-Chloro(and trifluoromethyl)quinolin-4-ylamino]phenol

1993 ◽  
Vol 46 (11) ◽  
pp. 1685 ◽  
Author(s):  
GB Barlin ◽  
SJ Ireland ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Reaction ◽  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
Derivatives Of

Syntheses are reported for mono- and di-Mannich base derivatives of 3-[7-chloro(and trifluoro-methyl)quinolin-4-ylamino]phenols by Mannich reaction on 3-[7-chloro(and trifluoromethyl )-quinolin-4-ylamino]phenols or by condensation of Mannich base derivatives of 3-aminophenol, prepared from 3-nitrophenol, with the appropriate 4-chloroquinoline. The antimalarial activity of 3-(7′-chloroquinolin-4′-ylamino)-2,6-bis[ pyrrolidin-1″-ylmethyl -(or piperidin-1″-ylmethyl)]phenol against the FC-27 isolate of Plasmodium falciparum was comparable to that of chloroquine, and it was not significantly diminished in tests against the chloroquine -resistant K-1 isolate.

Potential Antimalarials. XIV. Mono-Mannich Bases of 4-[7'-Bromo (and trifluoromethyl)-1',5'-naphthyridin-4'-yl-amino]-5,6,7,8-tetrahydronaphthalen-1-ols

1991 ◽  
Vol 44 (5) ◽  
pp. 677 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu ◽  
JH Yan
Keyword(s):  
Plasmodium Falciparum ◽  
Mannich Bases ◽  
Significant Activity ◽  
Mannich Reactions ◽  
Amino Compounds ◽  
In Vivo Tests ◽  
Sensitive Isolate ◽  
Plasmodium Vinckei

The mono- Mannich bases 2-diethylaminomethyl-, 2-t-butylaminomethyl-, 2-(pyrrolidin-1-ylmethyl)-, 2-(piperidin-1-ylmethyl)-, 2-(3-and 4-methylpiperidin-1-ylmethyl)-, 2-(4-benzylpip- eridin-1-ylmethyl)- and 2-(4-benzylpiperazin-1-ylmethyl)-4-[7-bromo (and 7-trifluoromethyl)- 1,5-naphthyridin-4-ylamino]-5,6,7,8-tetrahydronaphthalen-1-ols have been prepared from 4- acetamido-5,6,7,8-tetrahydronaphthalen-1-ols by Mannich reactions followed by hydrolysis to the 4-amino compounds and condensation with the relevant 4-chloro heterocycle. The antimalarial activities of these compounds against the chloroquine -sensitive isolate (FCQ-27) of Plasmodium falciparum in vitro are reported; 4-(7-bromo-1,5-naphthyridin-4-yl)amino-2-(t- butylaminomethyl )-5,6,7,8-tetrahydronaphthalen-1-ol was about twice as active as chloroquine . In in vivo tests against Plasmodium vinckei vinckei in mice this compound exhibited significant activity. The 7-bromo compounds were more active than their 7-trifluoromethyl analogues.

Potential Antimalarials. XIII. Mono-Mannich Bases of 4-[7-Chloro (and 7-trifluoromethyl)quinolin-4-ylamino] and 4-(7-Bromo-1,5-naphthyridin-4-ylamino)-3-methylphenol

1991 ◽  
Vol 44 (1) ◽  
pp. 151 ◽  
Author(s):  
GB Barlin ◽  
C Jiravinyu
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Mannich Bases

The preparation of di-Mannich bases derived from 4-[7-chloro(and 7-trifluoromethyl)quinolin-4-ylamino] and 4-(7-bromo-1,5-naphthyridin-4-ylamino)-3-methylphenol are reported. In tests for antimalarial activity against the FCQ-27 ( chloroquine -sensitive) and K-1 ( chloroquine -resistant) isolates of Plasmodium falciparum in vitro, the 3-methylphenols were shown to be less active than their demethyl analogues reported previously.

Synthesis and Antimalarial Activity Study of Some New Mannich Bases of 7-Chloro-4-Aminoquinoline

2013 ◽  
Vol 9 (3) ◽  
pp. 379-383 ◽  
Author(s):  
Susanta Roy ◽  
Dipak Chetia ◽  
Mithun Rudrapal ◽  
Anil Prakash
Keyword(s):  
Antimalarial Activity ◽  
Mannich Bases

scholarly journals Stage-dependent effect of deferoxamine on growth of Plasmodium falciparum in vitro

Blood ◽  
1990 ◽  
Vol 76 (6) ◽  
pp. 1250-1255 ◽  
Author(s):  
S Whitehead ◽  
TE Peto
Keyword(s):  
Plasmodium Falciparum ◽  
Growth Inhibition ◽  
Antimalarial Activity ◽  
Clinical Malaria ◽  
Inhibitory Effect ◽  
Parasite Development ◽  
And Control ◽  
Speed Of Onset

Abstract Deferoxamine (DF) has antimalarial activity that can be demonstrated in vitro and in vivo. This study is designed to examine the speed of onset and stage dependency of growth inhibition by DF and to determine whether its antimalarial activity is cytostatic or cytocidal. Growth inhibition was assessed by suppression of hypoxanthine incorporation and differences in morphologic appearance between treated and control parasites. Using synchronized in vitro cultures of Plasmodium falciparum, growth inhibition by DF was detected within a single parasite cycle. Ring and nonpigmented trophozoite stages were sensitive to the inhibitory effect of DF but cytostatic antimalarial activity was suggested by evidence of parasite recovery in later cycles. However, profound growth inhibition, with no evidence of subsequent recovery, occurred when pigmented trophozoites and early schizonts were exposed to DF. At this stage in parasite development, the activity of DF was cytocidal and furthermore, the critical period of exposure may be as short as 6 hours. These observations suggest that iron chelators may have a role in the treatment of clinical malaria.

scholarly journals In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

1996 ◽  
Vol 40 (9) ◽  
pp. 2094-2098 ◽  
Author(s):  
B Pradines ◽  
F Ramiandrasoa ◽  
L K Basco ◽  
L Bricard ◽  
G Kunesch ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Mechanism Of Action ◽  
Ribonucleotide Reductase ◽  
Antimalarial Activity ◽  
Iron Chelators ◽  
Resistant Clone ◽  
Iron Deprivation ◽  
Level Of Activity ◽  
Susceptible Clone

The activities of novel iron chelators, alone and in combination with chloroquine, quinine, or artemether, were evaluated in vitro against susceptible and resistant clones of Plasmodium falciparum with a semimicroassay system. N4-nonyl,N1,N8-bis(2,3-dihydroxybenzoyl) spermidine hydrobromide (compound 7) demonstrated the highest level of activity: 170 nM against a chloroquine-susceptible clone and 1 microM against a chloroquine-resistant clone (50% inhibitory concentrations). Compounds 6, 8, and 10 showed antimalarial activity with 50% inhibitory concentrations of about 1 microM. Compound 7 had no effect on the activities of chloroquine, quinine, and artemether against either clone, and compound 8 did not enhance the schizontocidal action of either chloroquine or quinine against the chloroquine-resistant clone. The incubation of compound 7 with FeCI3 suppressed or decreased the in vitro antimalarial activity of compound 7, while no effect was observed with incubation of compound 7 with CuSO4 and ZnSO4. These results suggest that iron deprivation may be the main mechanism of action of compound 7 against the malarial parasites. Chelator compounds 7 and 8 primarily affected trophozoite stages, probably by influencing the activity of ribonucleotide reductase, and thus inhibiting DNA synthesis.

Sign in / Sign up

Export Citation Format

Share Document