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. 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. 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.

scholarly journals In vitro antimalarial activity of some organotin(IV)2-nitrobenzoate compounds against Plasmodium falciparum

2018 ◽  
Vol 37 (2) ◽  
Author(s):  
Sutopo Hadi ◽  
Noviany Noviany ◽  
Mita Rilyanti
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Drug ◽  
Antimalarial Activity ◽  
Positive Control ◽  
Intermediate Products ◽  
Nitrobenzoic Acid ◽  
The Future ◽  
Ic50 Values

Antimalarial activity study of organotin(IV) derivatives with nitrobenzoic acid derivatives used as ligands has been performed. The targeted compounds were prepared from their organotin(IV) chlorides via dibutyltin(IV) oxide, diphenyltin(IV) dihydroxide, and triphenyltin(IV) hydroxide intermediate products, followed by reacting the intermediate products with 2-nitrobenzoic acid. The antimalarial activity was performed against P. falciparum. The results showed that the IC50values of dibutyiltin(IV) di-2-nitrobenzoate, diphenyltin(IV) di-2-nitrobenzoate, and triphenyltin(IV) 2-nitrobenzoate were in 8.4 × 10‑3, 5.3 × 10–2, and 9.1 × 10–3 µg/ml, respectively. The IC50 values were slightly higher than the value for chloroquine (2 × 10–3 µg/ml) used as the positive control; however, one advantage is that all prepared organotin(IV) compounds were not resistant to Plasmodium, making the use of organotin(IV) as an antimalarial is possible. The results indicated that the derivative of triphenyltin(IV) was more potent when used as an antimalarial, as expected, and has potential to be developed as an antimalarial drug in the future.

Potential Antimalarials. XV. Di-Mannich Bases of 2-(7'-Chloroquinolin-4'-ylamino)phenol and 2-[7'-Bromo( and trifluoromethyl)-1',5'-naphthyridin-4'-ylamino]phenol

1992 ◽  
Vol 45 (10) ◽  
pp. 1651 ◽  
Author(s):  
GB Barlin ◽  
TMT Nguyen ◽  
B Kotecka ◽  
KH Rieckmann
Keyword(s):  
Mannich Base ◽  
Antimalarial Activity ◽  
Mannich Bases ◽  
In Vitro Tests ◽  
In Vivo Tests ◽  
Methyl Derivatives ◽  
Derivatives Of ◽  
Plasmodium Vinckei

A total of 26 di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylamino)phenol and 2-[7'- bromo (and trifluoromethyl )-1',5'-naphthyridin-4'-ylino]phenol, such as 2-(7'-chloroquinolin- 4'-ylamino)-4,6-bis( piperidin-1″-ylmethyl )phenol, together with some 3- and 5-methyl derivatives and mono-Mannich analogues, have been prepared by condensation of the 4-chloro heterocycle with the appropriate Mannich base derivatives of 2-aminophenols. In in vitro tests against Plasmodium falciparum, many of the di-Mannich base derivatives of 2-(7'-chloroquinolin-4'-ylarnino)phenol exhibited activity comparable to or superior to chloroquine against the chloroquine -sensitive (FCQ-27) isolate, and vastly superior activity compared with chloroquine against the chloroquine -resistant (K-1) isolate. Strong antimalarial activity was also revealed in in vivo tests against Plasmodium vinckei vinckei in mice.

scholarly journals In vitro antimalarial activity of six Aspidosperma species from the state of Minas Gerais (Brazil)

2012 ◽  
Vol 84 (4) ◽  
pp. 899-910 ◽  
Author(s):  
Maria Fâni Dolabela ◽  
Salma G. Oliveira ◽  
José M. Peres ◽  
José M.S. Nascimento ◽  
Marinete M. Póvoa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Antimalarial Activity ◽  
Minas Gerais ◽  
The State ◽  
Active Compounds ◽  
Human Malaria ◽  
Plant Parts ◽  
Ic50 Values

Ethnomedicinal informations point to some Aspidosperma species (Apocynaceae) as antimalarial plants in Brazil and have motivated the evaluation of six species which were collected in the state of Minas Gerais: A. cylindrocarpon Müll. Arg., A. parvifolium A. DC., A. olivaceum Müll. Arg., A. ramiflorum Müll. Arg., A. spruceanum Benth. ex Müll. Arg. and A. tomentosum Mart.. A total of 23 extracts of different plant parts in different solvents were assayed in vitro against chloroquine-resistant (W2) and chloroquine-sensitive (3D7) strains of Plasmodium falciparum. All the extracts were shown to be active with IC50 values in the range of 5.0 ± 0 2.8 µg/mL to 65.0 ± 4.2 µg/mL. TLC profile of the extracts revealed the presence of alkaloids in the six species assayed. These results seem to confirm the popular use of Aspidosperma species to treat human malaria in Brazil and seem point to alkaloids as the putative active compounds of the assayed species.

Metal Complexes of Biologically Important Ligands, CXXV [1]. Palladium(II) and Platinum(II) Complexes of Quinine Derivatives and in vitro Tests

2000 ◽  
Vol 55 (9) ◽  
pp. 821-833 ◽  
Author(s):  
Roland Hubel ◽  
Tomas Jelinek ◽  
Wolfgang Beck
Keyword(s):  
Plasmodium Falciparum ◽  
Metal Complexes ◽  
Dicarboxylic Acid ◽  
Antimalarial Activity ◽  
Platinum Complexes ◽  
In Vitro Tests ◽  
Stoichiometric Ratio ◽  
Palladium And Platinum Complexes ◽  
Metal Ligand

Several quinine substituted derivatives at the C(9)-O position (1 - 7) have been obtained from quinine and N-protected glycine chloride, chlorocarbonyl ferrocene, phenylisocyanate, dicarboxylic acid dichlorides or trimesinic trichloride. From these only the glycine derivative 1 showed significant antimalarial activity in in vitro tests against Plasmodium falciparum isolates. The quinine derivatives were used as ligands and from chloro bridged palladium and platinum complexes Cl(R3P)M(μ-Cl)2M(PR3)Cl (M = Pd, Pt) di-, tri-, tetra- and hexametallic compounds 8-21 with coordination both of the aliphatic and aromatic N-atoms were synthesized. Protection of the tertiary N atom by protonation gave the quinoline complexes 22-25. Using a stoichiometric ratio metal/ligand = 1/1 it could be shown that the coordination of metal ions at the quinoline N-atom is by far preferred. A titanium(IV) complex 36 is formulated as [Ti(quinine)3Cl]Cl3 with quinine as a zwitterionic ligand

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.

Discovery of 3-Cinnamamido-N-Substituted Benzamides as Potential Antimalarial Agents

2020 ◽  
Vol 16 ◽  
Author(s):  
Haicheng Liu ◽  
Yushi Futamura ◽  
Honghai Wu ◽  
Aki Ishiyama ◽  
Taotao Zhang ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Antimalarial Activity ◽  
In Vitro Assays ◽  
Compound Library ◽  
Antimalarial Agents ◽  
Phenotypic Screen ◽  
Ic50 Values ◽  
Substituted Benzamides

Background: Malaria is one of the most devastating parasitic diseases, yet the discovery of antimalarial agents remains profoundly challenging. Very few new antimalarials have been developed in the past 50 years, while the emergence of drug-resistance continues to appear. Objective: This study focuses on the discovery, design, synthesis, and antimalarial evaluation of 3-cinnamamido-N-substituted benzamides. Method: In this study, a screening of our compound library was carried out against the multidrug-sensitive Plasmodium falciparum 3D7 strain. Derivatives of the hit were designed, synthesized and tested against P. falciparum 3D7 and the in vivo antimalarial activity of the most active compounds was evaluated using the method of Peters’ 4-day suppressive test. Results: The retrieved hit compound 1 containing a 3-cinnamamido-N-substituted benzamide skeleton showed moderate antimalarial activity (IC50 = 1.20 µM) for the first time. A series of derivatives were then synthesized through a simple four-step workflow, and half of them exhibited slightly better antimalarial effect than the precursor 1 during the subsequent in vitro assays. Additionally, compounds 11, 23, 30 and 31 displayed potent activity with IC50 values of approximately 0.1 µM, and weak cytotoxicity against mammalian cells. However, in vivo antimalarial activity is not effective which might be ascribed to the poor solubility of these compounds. Conclusion: In this study, phenotypic screen of our compound library resulted in the first report of 3-cinnamamide framework with antimalarial activity and 40 derivatives were then designed and synthesized. Subsequent structure-activity studies showed that compounds 11, 23, 30 and 31 exhibited the most potent and selective activity against P. falciparum 3D7 strain with IC50 values around 0.1 µM. Our work herein sets another example of phenotypic screen-based drug discovery, leading to potentially promising candidates of novel antimalarial agents once given further optimization.

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.

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