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

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.

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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

Australian Journal of Chemistry ◽

10.1071/ch9921845 ◽

1992 ◽

Vol 45 (11) ◽

pp. 1845 ◽

Cited By ~ 2

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.

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Sintesis dan Evaluasi Antimalaria In Vitro Turunan Kinin Terhadap Plasmodium falciparum

Jurnal Kefarmasian Indonesia ◽

10.22435/jki.v11i2.3923 ◽

2021 ◽

Vol 11 (2) ◽

pp. 109-120

Author(s):

Salahuddin Salahuddin ◽

Rahmana Emran K ◽

Muhammad Hanafi ◽

Andini Sundowo ◽

Puspa Dewi NL ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Drug ◽

Malaria Treatment ◽

Reaction Products ◽

Synthetic Product ◽

13C Nuclear Magnetic Resonance ◽

Ic50 Value ◽

Ic50 Values

Nowadays kinin is the most effective antimalarial drug and its used as an alternative in malaria treatment. However, toxicity of quinine restrict its use as an antimalarial drug. Lipophilicity and long half-life (t½) of quinine that reach 10-20 hours are responsible for its toxicity. The aim of this research is to obtain more polar quinine derivatives by means of hydrogen peroxide reactions to reduce the toxicity. The reactions using hydrogen peroxyde is performed analogously to the procedures reported in the literature. Extract of pure anhydrous kinin is purified in coloumn chromatography followed by structure elucidation. Synthetic product is tested in vitro against Plasmodium falciparum. The characterization of reaction products is performed with proton (1H) and carbon 13 (13C) nuclear magnetic resonance (NMR) spectroscopy. It showed that the reaction using reagents led to epoxidation of vinyl substituents of chinuclidine ring with 61,08% yields. Antimalarial test against Plasmodium falciparum obtained 1.250-2.500 μg/mL of IC50 value. The IC50 values indicated that the synthesis products were not potential for malaria treatment.

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

Anais da Academia Brasileira de Ciências ◽

10.1590/s0001-37652012000400005 ◽

2012 ◽

Vol 84 (4) ◽

pp. 899-910 ◽

Cited By ~ 15

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.

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Phytochemical, Biological and Computational Investigations of Erythrina fusca Lour. to Assess Antimalarial Property against Plasmodium falciparum

10.20944/preprints202010.0576.v1 ◽

2020 ◽

Author(s):

Saiful Arefeen Sazed ◽

Ohedul Islam ◽

Sarah L. Bliese ◽

Muhammad Riadul Haque Hossainey ◽

Mahfuza Afroz Soma ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Antimalarial Drug ◽

Antimalarial Activity ◽

Drug Candidate ◽

Separation And Purification ◽

Membrane Stabilization ◽

Phytochemical Investigation ◽

Biological Tests

For centuries medicinal plants have been traditionally used for prophylaxis and ailment of diseases. Nowadays it’s easy to isolate, purify, and characterize bioactive compounds with high efficacy. To investigate the medicinal especially antimalarial property of traditionally used plants, a number of Erythrina spp have been reviewed systematically where Erythrina fusca has been selected for further analysis. Phytochemical investigation included chromatographic separation and purification of compounds followed by characterization using NMR. In-vitro antimalarial drug sensitivity ELISA was carried out against chloroquine (CQ) sensitive 3D7 and resistant Dd2 strains. Additional biological tests such as central and peripheral analgesic, antioxidant, anti-diarrheal, hypoglycemic, thrombolytic, and membrane stabilization activities were also investigated. Molecular docking was performed using the isolated compounds against clinically important 14 Plasmodium falciparum proteins. For the first time, Phaseolin, Phytol, β-amyrin, Lupeol, and Stigmasterol are reported here and extracts showed significant antimalarial activity against 3D7 and Dd2 strains (IC50 4.94-22 µg/mL). Potent central analgesic, antioxidant and anti-diarrheal activities (p&lt;0.05) and mild thrombolytic and membrane stabilization properties were also observed. Molecular docking of Phaseolin bolsters its potential as a new antimalarial drug candidate. This study projects significant medicinal values and necessitates further investigations to reveal its potential as a novel source of therapeutics.

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Antimalarial Activity of Some Organotin(IV) Chlorobenzoate Compounds against Plasmodium falciparum

Mediterranean Journal of Chemistry ◽

10.13171/mjc0200312162sh ◽

2020 ◽

Vol 10 (3) ◽

pp. 213-219

Author(s):

Sutopo Hadi ◽

Mona Dwi Fenska ◽

Rama Aji Wijaya ◽

Noviany Noviany ◽

Tati Suhartati

Keyword(s):

Plasmodium Falciparum ◽

Comparative Study ◽

Antimalarial Activity ◽

Positive Control ◽

Chlorobenzoic Acid ◽

Intermediate Products ◽

The Comparative Study

This paper reported the comparative study on antimalarial activity of some organotin(IV) derivatives with some chlorobenzoic acid derivatives used as the ligands. The compounds were synthesized by reacting the intermediate products of dibutyltin(IV) oxide, diphenyltin(IV) dihydroxide and triphenyltin(IV) hydroxide, with chlorobenzoic acid. The antimalarial activity was performed against Plasmodium falciparum. The results showed that the IC50 of the compounds tested were about the same with the chloroquine (2 x 10-3 µg/mL) used as the positive control, but unlike chloroquine which has been known to have resistance as antimalarial, these organotin(IV) compounds prepared are not resistant to the Plasmodium. The result also showed that the derivative of triphenyltin(IV) has higher IC50respective to others.

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

Medicinal Chemistry ◽

10.2174/1573406416666200817160708 ◽

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.

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

Blood ◽

10.1182/blood.v76.6.1250.1250 ◽

1990 ◽

Vol 76 (6) ◽

pp. 1250-1255 ◽

Cited By ~ 36

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.

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In vitro activities of novel catecholate siderophores against Plasmodium falciparum.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.40.9.2094 ◽

1996 ◽

Vol 40 (9) ◽

pp. 2094-2098 ◽

Cited By ~ 13

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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Antimalarial Effect of the Total Glycosides of the Medicinal Plant, Ranunculus japonicus

Pathogens ◽

10.3390/pathogens10050532 ◽

2021 ◽

Vol 10 (5) ◽

pp. 532

Author(s):

Hae-Soo Yun ◽

Sylvatrie-Danne Dinzouna-Boutamba ◽

Sanghyun Lee ◽

Zin Moon ◽

Dongmi Kwak ◽

...

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Plasmodium Berghei ◽

Antimalarial Activity ◽

Hematological Parameters ◽

Significant Inhibition ◽

Ic50 Values ◽

The Republic

In traditional Chinese medicine, Ranunculus japonicus has been used to treat various diseases, including malaria, and the young stem of R. japonicus is consumed as a food in the Republic of Korea. However, experimental evidence of the antimalarial effect of R. japonicus has not been evaluated. Therefore, the antimalarial activity of the extract of the young stem of R. japonicus was evaluated in vitro using both chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) strains; in vivo activity was evaluated in Plasmodium berghei-infected mice via oral administration followed by a four-day suppressive test focused on biochemical and hematological parameters. Exposure to extracts of R. japonicus resulted in significant inhibition of both chloroquine-sensitive (3D7) and resistant (Dd2) strains of P. falciparum, with IC50 values of 6.29 ± 2.78 and 5.36 ± 4.93 μg/mL, respectively. Administration of R. japonicus also resulted in potent antimalarial activity against P. berghei in infected mice with no associated toxicity; treatment also resulted in improved hepatic, renal, and hematologic parameters. These results demonstrate the antimalarial effects of R. japonicus both in vitro and in vivo with no apparent toxicity.

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