Synthesis and antiplasmodial evaluation of novel chromeno[2,3-b]chromene derivatives

Devakaram, Ruth; Black, David StC.; Choomuenwai, Vanida; Davis, Rohan A.; Kumar, Naresh

doi:10.1016/j.bmc.2011.12.037

Cited by 32 publications

(13 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is known that a wide range of medicinal plants (used since more than 1000 years ago) contain high levels of coumarins [ 7 ]. These compounds have become indispensable structural units that are useful in medicinal chemistry, displaying anticancer [ 8 ], antioxidant [ 9 ], anti-plasmodial [ 10 ], anti-malarial [ 11 ], anti-rhinovirus [ 12 ], antifungal [ 13 ] and antibacterial activity [ 14 ]. Much research has been focused on the inhibition of bacterial growth by naturally occurring coumarins such as xanthoxin, herniarin, umbelliferone and scopoletin.…”

Section: Introductionmentioning

confidence: 99%

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

Tiwari¹,

Seijas

Vázquez-Tato

et al. 2017

Molecules

View full text Add to dashboard Cite

The work reports the synthesis under solvent-free condition using the ionic liquid [Et3NH][HSO4] as a catalyst of fifteen novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)-methyl)-4-hydroxy-2H-chromen-2-onederivatives 4a–o as potential antimicrobial agents. The structures of the synthesized compounds were confirmed by IR, 1H-NMR, 13C-NMR, mass spectral studies and elemental analyses. All the synthesized compounds were evaluated for their in vitro antifungal and antibacterial activity. The compound 4k bearing 4-hydroxy-3-ethoxy group on the phenyl ring was found to be the most active antifungal agent. The compound 4e bearing a 2,4-difluoro group on the phenyl ring was found to be the most active antibacterial agent. The mode of action of the most promising antifungal compound 4k was established by an ergosterol extraction and quantitation assay. From the assay it was found that 4k acts by inhibition of ergosterol biosynthesis in C. albicans. Molecular docking studies revealed a highly spontaneous binding ability of the tested compounds to the active site of lanosterol 14α-demethylase, which suggests that the tested compounds inhibit the synthesis of this enzyme. The synthesized compounds were analyzed for in silico ADMET properties to establish oral drug like behavior and showed satisfactory results. To establish the antimicrobial selectivity and safety, the most active compounds 4e and 4k were further tested for cytotoxicity against human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 4e and 4k and results indicated that the compounds are non-toxic.

show abstract

Section: Introductionmentioning

confidence: 99%

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

Tiwari¹,

Seijas

Vázquez-Tato

et al. 2017

Molecules

View full text Add to dashboard Cite

show abstract

“…Coumarins are an elite class of naturally occurring compounds with promising therapeutic perspectives [ 6 , 7 ]. This compound has become obligatory structural unit that is utilitarian in medicinal chemistry, with a wide variety of activities such as anticancer [ 8 ], antioxidant [ 9 ], antiplasmodial [ 10 ], antimalarial [ 11 ], antirhinovirus [ 12 ], antifungal [ 13 ] and antibacterial properties [ 14 ]. 4-oxo-4H-Chromen-3-carbaldehyde (3-formylchromone) is a most significant starting point for the synthesis of quite a lot of biologically active compounds due to the existence of an unsaturated keto functional group, a conjugated second carbonyl group at the C-3 position, and an electrophilic centre at the C-2 position.…”

Section: Introductionmentioning

confidence: 99%

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study

Tiwari¹,

Seijas

Vázquez-Tato

et al. 2018

Molecules

View full text Add to dashboard Cite

Herein, we report an environmentally friendly, rapid, and convenient ionic liquid ([Et3NH][HSO4])-promoted facile synthesis of ethyl 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives 4(a–f) and 4-(6-substituted-4-oxo-4H-chromen-3-yl)-6-methyl-2-thioxo/oxo-1,2,3,4-tetrahydropyrimidine-5- carbohydrazide derivatives 6(a–f). All the synthesized derivatives 4(a–f) and 6(a–f) were evaluated for their in vitro antifungal and antibacterial activity, by method recommended by National Committee for Clinical Laboratory Standards (NCCLS). The compound 6c bearing a fluoro group on the chromone ring and oxygen and a hydrazino group (–NHNH2) on the pyrimidine ring, was found to be the most potent antibacterial compound amongst the synthesized derivatives. The compound 6f bearing a methoxy group (–OCH3) on the chromone ring and sulphur group on the pyrimidine ring, was found to exhibit equipotent antifungal activity when compared with the standard drug miconazole. A d-alanine-d-alanine ligase (DdlB) enzyme assay study and an ergosterol extraction and quantitation assay study were performed to predict the mode of action of the synthesized compounds. A molecular docking study was performed to predict the binding interactions with receptors and mode of action of the synthesized derivatives. Further, analysis of the ADMET parameters for the synthesized compounds has shown that these compounds have good oral drug-like properties and can be developed as oral drug candidates. To establish the antimicrobial selectivity and safety, the most active compounds 6c and 6f were further tested for cytotoxicity against the human cancer cell line HeLa and were found to be non-cytotoxic in nature. An in vivo acute oral toxicity study was also performed for the most active compounds 6c and 6f and the results indicated that the compounds are non-toxic in nature.

show abstract

“…Oxygen atom-containing heterocyclic molecules are one of the main targets in drug design research. In particular, chromene compounds are well known as important components either in biologically active synthetic or natural compounds (Devakaram et al, 2012[ 16 ]; Iriti and Faoro, 2010[ 26 ]; Juan et al, 2001[ 29 ]; Ren et al, 2011[ 48 ]). Certain natural and synthetic chromene analogues have shown a diversity of interesting properties over the years (Ali et al, 2015[ 5 ]; Cai et al, 2006[ 11 ]; Cheng et al, 2003[ 14 ]; Jain et al, 2009[ 28 ]; Kamdar et al, 2010[ 30 ]; Kemnitzer et al, 2008[ 31 ]; Mladenovic et al, 2011[ 40 ]; Mori et al, 2006[ 41 ]; Thareja et al, 2010[ 60 ]).…”

Section: Introductionmentioning

confidence: 99%

Structure-activity relationships and molecular docking studies of chromene and chromene based azo chromophores: a novel series of potent antimicrobial and anticancer agents

Afifi

Okasha

Ahmed

et al. 2017

EXCLI Journal; 16:Doc868; ISSN 1611-2156

View full text Add to dashboard Cite

Synthesis and antiplasmodial evaluation of novel chromeno[2,3-b]chromene derivatives

Cited by 32 publications

References 23 publications

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

Facile Synthesis of Novel Coumarin Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study, ADMET Prediction and Toxicity Study

Ionic Liquid-Promoted Synthesis of Novel Chromone-Pyrimidine Coupled Derivatives, Antimicrobial Analysis, Enzyme Assay, Docking Study and Toxicity Study

Structure-activity relationships and molecular docking studies of chromene and chromene based azo chromophores: a novel series of potent antimicrobial and anticancer agents

Contact Info

Product

Resources

About