Synthesis of hybrid 4-anilinoquinoline triazines as potent antimalarial agents, their in silico modeling and bioevaluation as Plasmodium falciparumtransketolase and β-hematin inhibitors

Sharma, Moni; Chauhan, Kuldeep; Chauhan, Shikha S.; Kumar, Ashok; Singh, Sweta; Saxena, Jitendra Kumar; Agarwal, Pooja; Srivastava, Kumkum; Kumar, Santosh; Puri, Sunil K.; Shah, Priyanka; Siddiqi, Mohammad Imran; Chauhan, Prem M. S.

doi:10.1039/c1md00188d

Cited by 46 publications

(35 citation statements)

References 60 publications

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“…Azoles are an important class of nitrogen containing heterocyclic compounds laced with various biological activities [25, [61][62][63][64][65][66][67][68][69][70][71][72][73][74]. Inclusion of such heterocyclic molecules is often known to enhance the biological activities and malaria is not the exception of it.…”

Section: Modification At N-alkyl Amino Side Chainmentioning

confidence: 99%

“…Thus, workers should work on this problem so that we can have a new armor. Sharma et al [68] studied the effect of removal of lateral side chain (flexible linker) of CQ by triazine (a rigid one) (compound 23, Figure 15). This change in side chain resulted into discovery of compounds having higher activity than standard drug CQ.…”

Section: Modification At N-alkyl Amino Side Chainmentioning

confidence: 99%

“…Amodiaquine is an example of such structural modification [27,[68][69][70]. Most of the compounds synthesized were having either better activity than CQ or comparable to it (1.36 to 45.21 ngmL -1 ).…”

Section: Modification At N-alkyl Amino Side Chainmentioning

confidence: 99%

See 2 more Smart Citations

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Mushtaque¹,

Shahjahan²

2015

European Journal of Medicinal Chemistry

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Section: Modification At N-alkyl Amino Side Chainmentioning

confidence: 99%

Section: Modification At N-alkyl Amino Side Chainmentioning

confidence: 99%

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Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Mushtaque¹,

Shahjahan²

2015

European Journal of Medicinal Chemistry

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“…Cytotoxicity Assay. Cytotoxicity of the compounds was determined using Vero cell line (C1008; Monkey kidney fibroblast) following the method as mentioned in the work of Sharma et al 34 The cells were incubated with compounddilutions for 72 h and MTT (SIGMA) was used as reagent for detection of cytotoxicity. Podophyllotoxin (SIGMA) was used as the reference drug.…”

Section: Journal Of Chemical Information and Modelingmentioning

confidence: 99%

In Silico Exploration for New Antimalarials: Arylsulfonyloxy Acetimidamides as Prospective Agents

Verma

Debnath

Agarwal

et al. 2015

J. Chem. Inf. Model.

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A strategy is described to identify new antimalarial agents to overcome the drug resistance and/or failure issues through in silico screening of multiple biological targets. As a part of this, three enzymes namely CTPS, CK, and GST were selected, from among 56 drug targets of P. falciparum, and used them in virtual screening of ZINC database entries which led to the design and synthesis of arylsulfonyloxy acetimidamides as their consensus inhibitors. From these, two compounds showed good activity against sensitive (3D7; IC50, 1.10 and 1.45 μM) and resistant (K1; IC50, 2.10 and 2.13 μM) strains of the parasite, and they were further investigated through docking and molecular dynamics simulations. The findings of this study collectively paved the way for arylsulfonyloxy acetimidamides as a new class of antimalarial agents.

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“…For example, the scaffold has been targeted to, among others, VEGFR2, EphB4, JAK2, Aurora A, FAK, and PKC theta [12][13][14][15][16][17]. [20]. 4-Anilino-Quinazolines and Analogs; 4-Amino-Quinolines 4-anilino-quinazolines are one of the earliest kinase scaffolds to be reported in the literature, and a recent review on this class and analogs is available [18].…”

Section: 4-diaminopyrimidinesmentioning

confidence: 99%

Kinase Inhibitors Among Hits from Malaria Cellular Screens

Brown

Drewry

Gamo

et al. 2013

Protein Phosphorylation in Parasites

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Tens of thousands of small molecules possessing potent inhibitory activity against Plasmodium falciparum blood stages have recently been disclosed by several groups. One of those published sets of hits has been named the Tres Cantos Antimalarial Set (TCAMS), and is composed of 13 533 individual compounds, most of them with submicromolar IC 50 -values against parasites growing in vitro. The molecular basis of their antimalarial action on the parasite or the infected erythrocyte is for the most part unknown. A minority of the compounds originated in drug discovery projects directed against defined human proteins, and computational analyses have suggested some level of enrichment among TCAMS hits of inhibitors acting against certain human targets, most notably protein and lipid kinases. This suggests that the antimalarial targets for such compounds could be the Plasmodium orthologs of those kinases. In this chapter the existing information on protein and phosphatidylinositol kinase inhibitors present in the TCAMS is revised and expanded, and the compounds are grouped into chemical families. Their structural similarity to inhibitors currently used in the clinical setting, or which are being developed as drug leads, are also exemplified. The most probable phylogenetic and homology relationships between P. falciparum kinases and human enzymes are updated and the known human targets of TCAMS compounds mapped onto their closest orthologs in the parasite's kinome. This information can be used to generate target hypotheses for the antimalarial mode of action of the compounds. Finally, some experimental approaches are outlined that can be deployed to test theoretical target predictions and to generate alternative hypotheses, which can be corroborated in live parasites.Ã Corresponding Author

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Synthesis of hybrid 4-anilinoquinoline triazines as potent antimalarial agents, their in silico modeling and bioevaluation as Plasmodium falciparumtransketolase and β-hematin inhibitors

Cited by 46 publications

References 60 publications

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

Reemergence of chloroquine (CQ) analogs as multi-targeting antimalarial agents: A review

In Silico Exploration for New Antimalarials: Arylsulfonyloxy Acetimidamides as Prospective Agents

Kinase Inhibitors Among Hits from Malaria Cellular Screens

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