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

Abstract

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.

Peel Extract Associated Oxidative Green Dakin Synthesis of Some Phenols Using Aqueous Banana Extract Catalyst

“…In the continuation of our previous work [11][12][13][14][15][16][17][18][19][20][21][22][23] , it was confirmed that until now none of the methods had used such a mild and green catalyst and solvents for Dakin oxidation. The designed method is suitable for the conversion of substituted benzaldehydes to its consequent substituted phenols.…”

Auto QSAR‐ A Fast Approach for Creation and Application of QSAR Models through Automation

“…[a] Molecular weight of the molecule, [b] Predicted octanol/water partition co‐efficient log P (acceptable range: −2.0 to 6.5) ,. [c] Predicted aqueous solubility; S in mol/L (acceptable range: −6.5 to 0.5).…”

Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone

“…Thus, the three-component condensation of 3-formylchromones 1, urea, and -ketoesters was used to synthesize a series of (chromonyl)tetrahydropyrimidines 116. [124][125][126] To catalyze the Biginelli reaction the following catalysts were used: TsOH, 124 sulfonic acid-functionalized mesoporous silica (MCM-41-SO 3 H), 125 and ionic liquid (triethylammonium hydrosulf-ate). 126 Hydrazides 117 were synthesized by heating the corresponding ethyl esters 116 with hydrazine hydrate in the presence of triethylammonium hydrosulfate under solvent-free conditions.…”

“…[124][125][126] To catalyze the Biginelli reaction the following catalysts were used: TsOH, 124 sulfonic acid-functionalized mesoporous silica (MCM-41-SO 3 H), 125 and ionic liquid (triethylammonium hydrosulf-ate). 126 Hydrazides 117 were synthesized by heating the corresponding ethyl esters 116 with hydrazine hydrate in the presence of triethylammonium hydrosulfate under solvent-free conditions. 126 Compounds 116 and 117 were screened for their antituberculosis and antitumor activities.…”

“…126 Hydrazides 117 were synthesized by heating the corresponding ethyl esters 116 with hydrazine hydrate in the presence of triethylammonium hydrosulfate under solvent-free conditions. 126 Compounds 116 and 117 were screened for their antituberculosis and antitumor activities. Raju et al demonstrated that activity of compound 116 (R 1 = Ph, R 2 = R 3 = H, R 4 = CF 3 , R 5 = Et) against M. tuber culosis H37Rv is comparable to that of the standard drugs Ethambutol and Ciprofl oxacin and cytotoxicity of derivative 116 (R 1 = R 2 = H, R 3 = NO 2 , R 4 = Me, R 5 = Et) against human neuroblastoma cell line SK-N-SH is similar to that of the reference drug Doxorubicin.…”