Significance of Microwave Irradiation in Synthesis of Thiazolidin-4-one Bearing Pyrimidine Analogues: Their in vitro Antimicrobial, Antituberculosis and Antimalarial Studies

Aim: To synthesise biologically active thiazolidin-4-one by microwave irradiation method and evaluate against different species of bacteria, fungi and Plasmodium falciparum. Background: Microwave irradiation method is serviceable for rapid and sustainable synthesis. In this present study, Thiazolidin-4-one bearing pyrimidine derivatives have been synthesized by microwave irradiation method. Objective: Thiazolidin-4-one is a valuable motif because of its broad-spectrum biological evaluation. It is famous for many types of biological profiles, mainly antimicrobial, anti-tuberculosis, anti- convulsant, antihypertensive, hypoglycemic agent and antimalarial. This biological response leads our attention towards the change of Thiazolidin-4-one skeleton to enhance potential. Present study aims to carry out a rapid synthesis of Thiazolidin-4-one derivative of pyrimidine by microwave- assisted heating. Methods: 4-(4-substituted phenyl)-6-(substituted aryl) pyrimidin-2-amine was the key intermediate required for the synthesis of 3-(4-(Substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl)-2-(4-hydroxy phenyl) thiozolidin-4-one (5A-J), which was prepared by using microwave irradiation. The structures of all newly synthesized motifs were characterized by spectral analysis (IR, 1H NMR, 13C NMR spectroscopy) and screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus pyogenes; antifungal activity against Candida albicans, Aspergillus niger, Aspergillus Clavatus; anti-tuberculosis activity against M. tuberculosis H37RV and antimalarial activity against Plasmodium falciparum. Results: Higher yield with less time-consuming method is the main advantage of Thiazolidin- 4-one bearing pyrimidine motifs synthesis. The excellent biological response of compounds 5B, 5C, 5D, 5G, 5H, 5I, and 5J was observed. Conclusion: As compared to conventional method, less time is required for the preparation of Thiazolidin- 4-one analogues by using advantageous microwave irradiation method. Thiazolidin-4-one derivatives showed improved biological activity.

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Synthesis and Biological Evaluation of Some Novel Quinoline based Chalcones as Potent Antimalarial, Anti-inflammatory, Antioxidant and Antidiabetic Agents

Asian Journal of Chemistry ◽

10.14233/ajchem.2020.22542 ◽

2020 ◽

Vol 32 (4) ◽

pp. 959-964

Author(s):

Nargisbano A. Peerzade ◽

Shravan Y. Jadhav ◽

Raghunath B. Bhosale

Keyword(s):

Antimalarial Activity ◽

Biological Activities ◽

13C Nmr Spectroscopy ◽

Biological Evaluation ◽

New Drugs ◽

Antidiabetic Activity ◽

High Yield ◽

Excellent Activity ◽

Anti Inflammatory

The objective of the present study was to synthesize a series of some novel quinoline based methoxy substituted chalcones and to evaluate their in vitro antimalarial, anti-inflammatory, antioxidant and antidiabetic activitites. The quinoline based chalcones was synthesized by condensation of 2-chloro-3-formyl qunoline with various methoxy substituted acetophenone in presence of NaOH. The Claisen-Schmidt condensation gave high yield of quinoline based chalcones. Synthesis of 2-chloro-3-formyl quinoline was carried out by Vilsmeir-Haack reaction on acetanilide and 4-methoxy acetanilide which on cyclization along with formylation give corresponding 2-chloro-3-formyl quinoline. The synthesized compounds were screened for in vitro antimalarial, anti-inflammatory, antioxiadant and antidiabetic activities. The structures of the synthesized compounds were characterized by infrared, 1H NMR and 13C NMR spectroscopy. Compounds 1f and 1h showed highest antimalarial activity even more than standard chloroquine diphosphate. Compound 1a showed excellent activity whereas 1c and 1d showed potent anti-inflammatory activity as compared to standard diclofenac. On the other hand, compounds 1a and 1g showed excellent antioxidant activity for 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical while compound 1a showed highest inhibition of nitic oxide free radical (NO•) and compound 1h showed highest inhibition for super oxide radical (SOR) as well as highest antidiabetic activity as compared to standard acarbose. All quinolne based chalcones were synthesized in good yields and showed potential biological activities hence they may be helpful for the designing of new drugs.

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Microwave Irradiated Synthesis of Pyrimidine Containing, Thiazolidin-4-ones: Antimicrobial, Anti-tuberculosis, Antimalarial, and Anti-protozoa evaluation

Letters in Organic Chemistry ◽

10.2174/1570178619666220111124104 ◽

2022 ◽

Vol 19 ◽

Author(s):

Hetal I. Soni ◽

Navin B. Patel ◽

Rahul B. Parmar ◽

Manuel J. Chan- Bacab ◽

Gildardo River

Keyword(s):

Microwave Irradiation ◽

Antimalarial Activity ◽

Biological Activities ◽

Biological Response ◽

Main Concern ◽

Synthesis Time ◽

Time Period ◽

Save Energy ◽

New Compounds ◽

Tuberculosis Activity

Aim: This study aims to synthesize thiazolidine-4-one compounds with a pyrimidine nucleus and evaluate against different species of bacteria, fungi, protozoa, and the malaria parasite. Background: Microwave irradiation was the best method for synthesizing the thiazolidin-4-one ring system. It took only 15 minutes for synthesizing thiazolidin-4-one while the conventional method required 12 hours. The rapid reaction was the main concern of this research. Objective: Pyrimidine and Thiazolidin-4-one nucleus have broad-spectrum biological activity and when it is introduced with other hetero atoms containing moiety, many types of biological activities have been found; antimicrobial, anti-tuberculosis, anti-protozoa, antimalarial are the main activities. The activity of these compounds inspired us to do extra research on Thiazolidin-4-one fused pyrimidines with different functional groups. The aim of this is to synthesize a combination of these two ring systems in less time by using a microwave irradiation method and to evaluate new compounds for different bioactivity. Method: 2-(4-Chlorophenyl)-3-(4-(substituted phenyl)-6-(substituted aryl) pyrimidin-2-yl) thiazolidin-4-ones (6A-J) were synthesized by microwave irradiation to save energy and time. The structure of all newly synthesized motifs was characterized by spectral analysis (1H NMR, 13C NMR, IR, spectroscopy) and screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pyogenes, antifungal activity against Candida albicans, Aspergillus niger, Aspergillus clavatus, anti-tuberculosis activity against M. tuberculosis H37RV, antimalarial activity against Plasmodium falciparum and anti-protozoa activity against L. mexicana and T. cruzi. Result: Because of microwave irradiation synthesis, time period is very less for preparing the new compound. Biological response given by compounds 6B, 6C, 6D, 6E, 6G, 6H, and 6J was found excellent. Conclusion: Good yield with purity of the newly synthesized thiazolidine-4-one compounds obtained in less time by using microwave irradiation. The biological response of some of the compounds of this series was found excellent

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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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Diversification of quinoline-triazole scaffolds with CORMs: Synthesis, in vitro and in silico biological evaluation against Plasmodium falciparum

Journal of Inorganic Biochemistry ◽

10.1016/j.jinorgbio.2020.111328 ◽

2021 ◽

Vol 215 ◽

pp. 111328

Author(s):

Fatima-Zahra Ishmail ◽

Diana R. Melis ◽

Mziyanda Mbaba ◽

Gregory S. Smith

Keyword(s):

Plasmodium Falciparum ◽

In Silico ◽

Biological Evaluation

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Synthesis and in Vitro Antimalarial Activity of Alkyl Esters Gallate as a Growth Inhibitors of Plasmodium Falciparum

Oriental Journal Of Chemistry ◽

10.13005/ojc/340207 ◽

2018 ◽

Vol 34 (2) ◽

pp. 655-662 ◽

Cited By ~ 2

Author(s):

Ade Arsianti ◽

Hendry Astuti ◽

Fadilah Fadilah ◽

Daniel Martin Simadibrata ◽

Zoya Marie Adyasa ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Growth Inhibitors ◽

Alkyl Esters

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Synthesis, antimalarial activity evaluation and molecular docking studies of some novel dispiro-1,2,4,5-tetraoxanes

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i4.24532 ◽

2015 ◽

Vol 10 (4) ◽

pp. 917 ◽

Cited By ~ 1

Author(s):

Mukesh Kumar Kumawat ◽

Dipak Chetia

Keyword(s):

Plasmodium Falciparum ◽

Molecular Docking ◽

Resistant Strain ◽

Antimalarial Activity ◽

Binding Pocket ◽

Docking Studies ◽

Spectroscopic Techniques ◽

Molecular Docking Studies ◽

Activity Screening

Seven novel dispiro-1,2,4,5-tetraoxane derivatives were synthesized and characterized by a number of analytical and spectroscopic techniques. The molecules were subsequently screened for in vitro antimalarial activity against chloroquine resistant strain of Plasmodium falciparum (RKL-9). At antimalarial activity screening, two compounds, namely 5d (MIC = 15.6 µg/mL or 64.5 µM) and 5f (MIC = 15.6 µg/mL or 54.6 µM) were found to be about 1.5 times more potent against chloroquine resistant strain-RKL-9 compared to chloroquine (MIC = 25.0 µg/mL or 78.3 µM). Molecular docking studies of potent ligands were also performed in cysteine protease binding pocket residues of falcipain-2 as a target protein.

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In vitro toxin production by Fusarium solani f. sp. piperis

Fitopatologia Brasileira ◽

10.1590/s0100-41582003000300002 ◽

2003 ◽

Vol 28 (3) ◽

pp. 229-235 ◽

Cited By ~ 10

Author(s):

Maria de Lourdes R. Duarte ◽

Simon A. Archer

Keyword(s):

Fusarium Solani ◽

Biological Response ◽

Black Pepper ◽

Biologically Active ◽

Piper Nigrum ◽

Piper Betle ◽

Toxic Metabolites ◽

Culture Filtrates ◽

Detached Leaves

Fusarium solani f. sp. piperis (teleomorph: Nectria haematococca f. sp. piperis), causal agent of root rot and stem blight on black pepper (Piper nigrum), produces secondary metabolites with toxigenic properties, capable of inducing vein discoloration in detached leaves and wilting in transpiring microcuttings. Production of F. solani f. sp. piperis (Fsp) toxic metabolites reached a peak after 25 days of static incubation on potato sucrose broth at 25 ºC under illumination. Changes in the pH of the culture filtrate did not alter the effect of toxic metabolites. However, when the pH was changed before the medium had been autoclaved, a more intense biological response was observed, with an optimum at pH 6.0. Isolates that produced red pigments in liquid cultures were more efficient in producing biologically active culture filtrates than those which produced pink coloured or clear filtrates suggesting that these pigments could be related to toxigenic activity. Detached leaves of seven black pepper cultivars and Piper betle showed symptoms of vein discoloration after immersion in autoclaved and non-autoclaved Fsp culture filtrates indicating the thermostable nature of these toxic metabolites.

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Overexpression of Plasmodium falciparum M1 Aminopeptidase Promotes an Increase in Intracellular Proteolysis and Modifies the Asexual Erythrocytic Cycle Development

Pathogens ◽

10.3390/pathogens10111452 ◽

2021 ◽

Vol 10 (11) ◽

pp. 1452

Author(s):

Carolina C. Hoff ◽

Mauro F. Azevedo ◽

Adriana B. Thurler ◽

Sarah El Chamy Maluf ◽

Pollyana M. S. Melo ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Antimalarial Activity ◽

Fold Increase ◽

Cysteine Proteases ◽

Aminopeptidase Activity ◽

Lower Sensitivity ◽

Wild Type ◽

Erythrocytic Cycle ◽

Transgenic Parasite

Plasmodium falciparum, the most virulent of the human malaria parasite, is responsible for high mortality rates worldwide. We studied the M1 alanyl-aminopeptidase of this protozoan (PfA-M1), which is involved in the final stages of hemoglobin cleavage, an essential process for parasite survival. Aiming to help in the rational development of drugs against this target, we developed a new strain of P. falciparum overexpressing PfA-M1 without the signal peptide (overPfA-M1). The overPfA-M1 parasites showed a 2.5-fold increase in proteolytic activity toward the fluorogenic substrate alanyl-7-amido-4-methylcoumarin, in relation to the wild-type group. Inhibition studies showed that overPfA-M1 presented a lower sensitivity against the metalloaminopeptidase inhibitor bestatin and to other recombinant PfA-M1 inhibitors, in comparison with the wild-type strain, indicating that PfA-M1 is a target for the in vitro antimalarial activity of these compounds. Moreover, overPfA-M1 parasites present a decreased in vitro growth, showing a reduced number of merozoites per schizont, and also a decrease in the iRBC area occupied by the parasite in trophozoite and schizont forms when compared to the controls. Interestingly, the transgenic parasite displays an increase in the aminopeptidase activity toward Met-, Ala-, Leu- and Arg-7-amido-4-methylcoumarin. We also investigated the potential role of calmodulin and cysteine proteases in PfA-M1 activity. Taken together, our data show that the overexpression of PfA-M1 in the parasite cytosol can be a suitable tool for the screening of antimalarials in specific high-throughput assays and may be used for the identification of intracellular molecular partners that modulate their activity in P. falciparum.

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