Recent Advances in the Research of 2,3-Diaryl-1,3-thiazolidin-4-one Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

Tian, Ye; Zhan, Peng; Rai, Diwakar; Zhang, Jiyan; Clercq, Erik De; Liu, Xinyong

doi:10.2174/092986712800167383

Cited by 20 publications

(7 citation statements)

References 42 publications

(68 reference statements)

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“…Diverse biological activities have been described for heterocyclic thiazolidinones, including antimicrobial [34, 35], anti-fungal [36], anti-inflammatory [37], anti-tumour [38], anti-HIV [39], anti-Alzheimer’s disease as muscarinic receptor 1 agonist [40], and anti-malarial [41]. As for PQ-imidazolidinone derivatives, PQ-TZs are unlikely to act as pro-drugs because the thiazolidin-4-one ring is stable at low pH.…”

Section: Discussionmentioning

confidence: 99%

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

Aguiar

Figueiredo

Neuenfeldt

et al. 2017

Malar J

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BackgroundPrimaquine is an anti-malarial used to prevent Plasmodium vivax relapses and malaria transmission. However, PQ metabolites cause haemolysis in patients deficient in the enzyme glucose-6-phosphate dehydrogenase (G6PD). Fifteen PQ-thiazolidinone derivatives, synthesized through one-post reactions from primaquine, arenealdehydes and mercaptoacetic acid, were evaluated in parallel in several biological assays, including ability to block malaria transmission to mosquitoes.ResultsAll primaquine derivatives (PQ-TZs) exhibited lower cell toxicity than primaquine; none caused haemolysis to normal or G6PD-deficient human erythrocytes in vitro. Sera from mice pretreated with the test compounds thus assumed to have drug metabolites, caused no in vitro haemolysis of human erythrocytes, whereas sera from mice pretreated with primaquine did cause haemolysis. The ability of the PQ-TZs to block malaria transmission was evaluated based on the oocyst production and percentage of mosquitoes infected after a blood meal in drug pre-treated animals with experimental malaria caused by either Plasmodium gallinaceum or Plasmodium berghei; four and five PQ-TZs significantly inhibited sporogony in avian and in rodent malaria, respectively. Selected PQ-TZs were tested for their inhibitory activity on P. berghei liver stage development, in mice and in vitro, one compound (4m) caused a 3-day delay in the malaria pre-patent period.ConclusionsThe compound 4m was the most promising, blocking malaria transmissions and reducing the number of exoerythrocytic forms of P. berghei (EEFs) in hepatoma cells in vitro and in mice in vivo. The same compound also caused a 3-day delay in the malaria pre-patent period.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-017-1755-6) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

Aguiar

Figueiredo

Neuenfeldt

et al. 2017

Malar J

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“…苷类逆转录酶抑制剂具有高的抗 HIV-1 活性和选择性引起了广泛关注 [5] . 经系统的结构优化, 2-(2,6-二卤代苯基)-3-(4,6-二甲基嘧啶-2-基)噻唑烷-4-酮化合物 1～4 较其它芳基取代具有更高的抗 HIV 活性(图 1) [6～10] .…”

Section: 构类似物(图 1) 23-(二芳基)-13-噻唑烷-4-酮作为非核unclassified

Synthesis and Anti-HIV-RT Activity of Novel Thiazolindin-4-one Derivatives Possessing Hydrophilic Groups

陈华¹,

黄长军²,

朱墨³

et al. 2014

Chin. J. Org. Chem.

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A series of thiazolidin-4-one derivatives possessing ester were synthesized under microwave irradiation, and then the corresponding products with hydrophilic groups, like carboxyl and hydroxyl groups, were obtained after hydrolysis reaction or reduction reaction. The compounds were evaluated for their human immunodeficiency virus (HIV) reverse transcriptases inhibitory activities in vitro HIV-RT kit assay (colorimetric method). The results showed that some of the compounds, such as 8a, 8b, 9a, 9b and 14c, could effectively inhibit RT activity. Among them, compounds 8a and 9a where ethyl group existed at 5-position on N-3 pyrimidine ring were the best ones with the IC 50 values of 3.02 and 3.06 μmol•L -1 , respectively. Structure activity relationship analysis of these analogues suggested that the introduction of hydrophilic groups had little effect on their anti-HIV-RT activity and the N-3 pyrimidine moiety on thiazolidin-4-one ring should be more favorable to the anti-HIV activity than the C-2 phenyl group.

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“…Except of these drugs many other molecules have been found to display RT inhibitory action [7,8,9,10,11,12,13], among which are: benzothiazine dioxides [14], N1,N3-disubstituted uracils [15], 6-arylmethyl-substituted S-DABOs [16], adamantyl-substituted thiazolidine-4-ones [17,18] and many others [19,20,21,22,23,24,25,26,27]. The 2,3-diaryl-thiazolidin-4-one scaffold appeared as a selective NNRTI [28,29]. Modeling studies on the HIV-1 RT inhibitory activity of 2,3-diaryl-thiazolidin-4-ones showed the importance of overall hydrophobicity of the analogues and the presence of a heteroaryl system over the 3-aryl moiety for better HIV-1 RT inhibitory activity [30,31,32,33,34].…”

Section: Introductionmentioning

confidence: 99%

Novel Thiazolidin-4-ones as Potential Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

et al. 2019

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Background: HIV is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), an infectious disease with increasing incidence worldwide. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) play an important role in the treatment of AIDS. Although, many compounds are already being used as anti-HIV drugs, research for the development of new inhibitors continues as the virus develops resistant strains. Methods: The best features of available NNRTIs were taken into account for the design of novel inhibitors. PASS (Prediction of activity spectra for substances) prediction program and molecular docking studies for the selection of designed compounds were used for the synthesis. Compounds were synthesized using conventional and microwave irradiation methods and HIV RT inhibitory action was evaluated by colorimetric photometric immunoassay. Results: The evaluation of HIV-1 RT inhibitory activity revealed that seven compounds have significantly lower ΙC50 values than nevirapine (0.3 μΜ). It was observed that the activity of compounds depends not only on the nature of substituent and it position in benzothiazole ring but also on the nature and position of substituents in benzene ring. Conclusion: Twenty four of the tested compounds exhibited inhibitory action lower than 4 μΜ. Seven of them showed better activity than nevirapine, while three of the compounds exhibited IC50 values lower than 5 nM. Two compounds 9 and 10 exhibited very good inhibitory activity with IC50 1 nM.

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Recent Advances in the Research of 2,3-Diaryl-1,3-thiazolidin-4-one Derivatives as Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

Cited by 20 publications

References 42 publications

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

Primaquine-thiazolidinones block malaria transmission and development of the liver exoerythrocytic forms

Synthesis and Anti-HIV-RT Activity of Novel Thiazolindin-4-one Derivatives Possessing Hydrophilic Groups

Novel Thiazolidin-4-ones as Potential Non-Nucleoside Inhibitors of HIV-1 Reverse Transcriptase

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