Reaction of 2-imino-2H-chromene-3-carboxamide with some phosphorus esters: Synthesis of some novel chromenes containing phosphorus heterocycles and phosphonate groups and their antioxidant and cytotoxicity properties

Abstract

Novel chromenyl α-aminophosphonic acid 4 and dialkyl chromenyl phosphonate 6 have been obtained. In addition, some novel types of chromene fused with phosphorus heterocycles such as chromeno[4,3-c][1,2]azaphospholes 5 and 7, chromeno[2,3-d][1,3,2]diazaphosphinine 8 and 1,2-oxaphosphinino[3,4-c]pyridine 10 have been synthesized. The methodology depended on treatment of 2-imino-2H-chromene-3-carboxamide (1) with some phosphorus esters. The synthesized compounds were evaluated for antioxidant and cytotoxic activities. Among the synthesized compounds, compound 5 exhibited the most antioxidant activity with IC₅₀ = 2.8?μg/mL in comparison with ascorbic acid as standard antioxidant. Also, compound 5 had significant cytotoxic effects against four cancer cell lines. Its IC₅₀ values ranged between 4.96 and 7.44?μg/mL in comparison to doxorubicin (IC₅₀ = 0.426–0.493?μg/mL).     

Synthesis,nematicidal activity and docking study of novel chromone derivatives containing substituted pyrazole

A series of chromone derivatives containing substituted pyrazole were designed and synthesized. Preliminary bioassays showed that most of the synthesized compounds exhibited good nematicidal activity in vivo against Meloidogyne incognita at 10 mg/L.     

Synthesis,characterization, and antimicrobial evaluation of some novel anthracene heterocycles derivatives

A series of novel heterocyclic compounds containing anthracene moiety was synthesized. Reaction of (11R,15S)-9,10-dihydro-9,10-[3,4]furanoanthracene-12,14-dione with 2-cyanoacetohydrazide gave 2-cyano-pyrroloanthracen acetamide (1) , which acts as an adaptable material for the synthesis of new heterocyclic compounds. The synthesized compounds were examined for their antimicrobial activity against Escherichia coli and Staphylococcus aureus via p-iodonitrotetrazolium violet formazon assay. The results exhibited great activity against the tested strains with a minimum bactericidal concentration range from 0.636 to 3.8 mg/mL) and 0.159 to 3.6 mg/mL for E coli and S aureus, respectively. Interestingly, the highest activity was recorded for chromene derivative (6) against both strains.     

Synthesis and cytotoxicity of silylalkylthio‐substituted N‐heterocycles and their hydroselenites

New hydroselenites of the different silylalkylthio‐substituted N‐heterocycles have been prepared by the reaction of selenium dioxide with N‐heterocycles in an aqueous medium. Their structure was confirmed by ¹H, ¹³C, and ⁷⁷Se NMR data. Most of these silylalkylthio‐substituted N‐heterocycles and their hydroselenites have an expressed cytotoxic activity on the MG‐22A (mouse hepatoma), HT‐1080 (human fibrosarcoma), B16 (mouse melanoma), and Neuro 2A (mouse neuroblastoma) cell lines. Some of the hydroselenites exhibit free‐radical protection simultaneously with a high cytotoxic effect. The substances studied were also active in vivoagainst sarcoma S‐180. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of annulated dihydroisoquinoline heterocycles via their nitrogen ylides

3,4-Dihydro-6,7-dimethoxyisoquinoline-1-acetonitrile reacts with some α-bromoketones in dry benzene to give the corresponding isoquinolinium salts, which undergo intramolecular cyclization to give pyrrolo[2,1-a]isoquinolines. Cross-coupling of the latter compounds with some aryldiazonium chlorides resulted in the formation of 3-arylhydrazonopyrrolo[2,1-a]isoquinolines, 3-arylazopyrrolo[2,1-a]isoquinolines and 3-aryl-1,2,3-triazolo[5,1-a]isoquinolines, respectively. The structures of the products were established on the basis of their elemental and spectral analyses as well as X-ray single crystal studies.     

Synthesis of ferrocene annulated trifluoromethylated heterocycles with crispine and lamellarin skeletons

Ferrocene analogues of pyrrolo[2,1-a]isoquinoline alkaloids, 2-(trifluoromethyl)-5,6-dihydroferroceno[g]indolizine and 6-(trifluoromethyl)-8,9-dihydro-6H-chromeno[4,3-b]ferroceno[g]indolizines, were obtained in 44–65% yield via the Grob reaction between 1-nitro-1-(2,2,2-trifluoroethylidene)alkanes or 3-nitro-2-(trifluoromethyl)-2H-chromenes and 1-alkyl-3,4-dihydroferroceno[c]pyridines in 2-propanol at reflux.     

Synthesis and antimicrobial activity of novel phosphorus heterocycles with exocyclic p-C link

Several new class of phosphorus heterocyclic compounds containing exocyclic P-C link such as 6-(2'-chloroethyl)/(allyl)/(benzyl)-1,2,4,8,10,11-hexachloro-12H-dibenzo[d,g][1,3,2]dioxaphosphocin 6-oxides (5-7), 2-(2"-chloroethyl)/(allyl)-6-(1,1-dimethylethyl)-3-cyclohexyl-3,4-dihdro-2H-1,3,2-benzoxazaphosphorin 2-oxides (9, 10), 2-(2"-chloroethyl-2,3-dihydro-3-(4'-bromophenyl)-1H-naphth[1,2-e][1,3,2]-oxazaphosphorin 2-oxide (12), 2-(2"-chloroethyl)/(allyl)-2,3-dihydro-5-benzoyl-1H-1,3,2-benzodiazaphosphole 2-oxides (14, 15), 4-phenyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phosphapentalene 2-oxide (17) and 4-benzyl-2-(2"-chloroethyl)-1H-1,3,3a,5,6-pentaza-2-phospha-pentalene 2-oxide (19) were synthesized by reacting equimolar quantities of corresponding diol (4)/diamines (13, 16, 18), 2-cyclohexylaminomethyl-4-t-butylphenol (8) and 1-(4'-bromoanilinomethyl)-2-naphthol (11), with respective phosponyl dichlorides (1-3) in dry toluene/toluene-tetrahydro-furan/pyridine in the presence of triethylamine at various temperatures. Their structures were established by IR, (1)H-, (13)C- and (31)P-NMR spectral data. The mass spectral data were given for compounds 9, 12 and 15. The title compounds were screened for antibacterial activity against Staphylococcus aureus and Escherichia coli and antifungal activity on Aspergillus niger and Helminthosporium oryzae. Most of the compounds possess significant activity.     

Synthesis,characterization, DNA binding,DNA cleavage,antioxidant and in vitro cytotoxicity studies of ruthenium(II) complexes containing hydrazone ligands

The synthesis, spectral characterization, and biological studies of ruthenium(II) hydrazone complexes [RuCl(CO)(PPh₃)₂L] (where L = hydrazone ligands) have been carried out. The hydrazones are monobasic bidentate ligands with O and N as the donors and are preferably found in the enol form in all the complexes. The molecular structure of the ligands HL¹, HL²_, and HL³ were determined by single-crystal X-ray diffraction. The DNA binding studies of the ligands and complexes were carried out by absorption spectroscopic and viscosity measurements. The results revealed that the ligands and complexes bind to DNA via intercalation. The DNA cleavage activity of the complexes, evaluated by gel electrophoresis assay, revealed that the complexes are good DNA cleaving agents. The antioxidant properties of the complexes were evaluated against DPPH, OH, and NO radicals, which showed that the complexes have strong radical-scavenging. Further, the in vitro cytotoxic effect of the complexes examined on HeLa and MCF-7 cancer cell lines showed that the complexes exhibited significant anticancer activity.     

Synthesis and characterization studies of 3-formyl chromone Schiff base complexes and their application as antitumor,antioxidant and antimicrobial

A novel Schiff base namely (E)-3-((2,6-dihydroxypyrimidin-4-ylimino)methyl)-4H-chromen-4-one and its Co (II), N (II)i, Cu (II) and Cd (II) complexes have been synthesized and proved by elemental analysis, molar conductance, thermal analysis (TGA), Inductive Coupled plasma (ICP), magnetic moment measurements, X-ray powder diffraction, IR, EI-mass,¹H NMR, ¹³C NMR,UV–Vis. and ESR spectral studies. On the basis of these data, it is evident that the Schiff base acts as bidentate via oxygen atom of carbonyl group and azomethine nitrogen atom for Co (II) complex; monobasic bidentate ligand for Ni (II), Cu (II) and Cd (II) complexes via oxygen atom of hydroxyl group and nitrogen atom of pyrimidine ring. The results showed all complexes have octahedral geometry. The average particle size of the ligand and its complexes were found to be 1.010–0.343 nm. The pharmacological action (antioxidant, antimicrobial and anticancer) of the prepared compounds is studied. The antitumor activity of the ligand and its metal complexes is evaluated against human liver carcinoma (HEPG2) cell. The data displayed the Co (II) complexes strong cytotoxicity where IC₅₀ values of Co (II) complex and 5-fluorouracil (stander drug) are 9.33 and 7.86 μg/ml respectively. The Co (II) and Cd (II) complexes have antibacterial activity more than ampicillin (stander drug). The interaction of the synthesized compounds with calf-thymus DNA (CT-DNA) has been performed via absorption spectra and viscosity technique. The DNA- binding constants have been determined.     

Synthesis of novel substituted pyrano annulated flavones

A simple and efficient one pot method has been developed for the synthesis of some new functionalized pyrano fused flavone derivatives, alkyl 4,8-dioxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-10-carboxylates and dialkyl 4-oxo-2-phenyl-4,8-dihydropyrano[2,3-f]chromene-8,9-dicarboxylates, from 7-hydroxy flavones and 7-hydroxy 8-formyl flavones using dialkylacetalynedicarboxylates in the presence of triphenyl phosphine. The structures of all synthesized compounds were elucidated by FT-IR, ¹H and ¹³C NMR and Mass spectral analysis.     

Unusual behavior of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one towards some phosphorus reagents: Synthesis of novel diethyl 2-phosphonochromone,diethyl 3-phosphonopyrone and 1,3,2-oxathiaphosphinines

The chemical reactivity of 3-(dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one (1) towards some phosphorus reagents was studied. The enaminone 1 was cyclized into diethyl 2-phosphonochromone 2 via its treatment with diethyl phosphite in basic medium. However, its reaction with triethoxy phosphonoacetate gave the substituted pyrone phosphonate 3. In addition, two novel examples of 4-(dimethylamino)-6-(2-hydroxyphenyl)-2-sulfido-4H-1,3,2-oxathia-phosphinines 6 and 7 were obtained from treatment of enaminone 1 with O,O-diethyl dithiophosphoric acid and Lawesson’s reagent. When enaminone 1 was also treated with phosphorus decasulfide, it was turned into 4H-thiochromene-4-thione while its treatment with phosphorus tribromide, phosphorus oxychloride, or phenylphosphonic dichloride, 4H-4-oxo-chromene was isolated in all cases. The possible reaction mechanisms of the formation of these products were discussed. The structures of newly isolated products were established by elemental analysis and spectral tools.     

Synthesis and biological evaluation of some novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids as potential antifungal agents

In an effort to discover lead compounds that may be of importance as potent antifungal agents, a series of novel 1-alkyl-3-methylimidazolium carboxylate ionic liquids were efficiently synthesized through a solvent-free ultrasound-assisted quaternization reaction of 1-methylimidazole and alkyl bromides RBr (R = hexyl, octyl) followed by an anion exchange process with selected carboxylate anions (cinnamate, salicylate, crotonate, and oxalate). Quantitative yields obtained were in the range of 86–94%. Structure characterization was done using FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopic techniques. All the synthesized compounds showed in vitro antifungal activity against the fungus Candida albicans with the minimum inhibitory concentrations found to be less than or equal to 1%. Preliminary cytotoxicity assays (trypan blue exclusion and MTT) were performed on all ionic liquids and findings revealed higher lymphocyte viability in 1-hexyl-3-methylimidazolium carboxylate ionic liquids than in 1-octyl-3-methylimidazolium counterparts. No extensive toxicity effect was observed with the carboxylate anion variation. Among the tested compounds, 1-hexyl-3-methylimidazolium crotonate and 1-hexyl-3-methylimidazolium oxalate exhibited the lowest cytotoxicity in the trypan blue exclusion and MTT assays, respectively. Together, our results highlight the potential of carboxylate-based ionic liquids in the development of next-generation antifungal drugs.     

Synthesis and cytotoxic evaluation of novel simplified plinabulin-quinoline derivatives

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Synthesis of novel mercury heterocycles

Ortho-mercurated 4-aryloxymethylcoumarins and 1-azacoumarins have been found to undergo smooth intramolecular metalation in refluxing xylene in the presence of activated neutral alumina and anhydrous potassium carbonate. This is the first report on the synthesis of heterocycles not possessing a metal heteroatom linkage.     

Isolation and biological evaluation of chromone alkaloid dysoline,a new regioisomer of rohitukine from Dysoxylum binectariferum

The chromone alkaloid dysoline (1), a new regioisomer of rohitukine (2) along with rohitukine and rohitukine-N-oxide (3) were isolated from the stem barks of Dysoxylum binectariferum. The structure of dysoline (1) was determined by extensive 2D-NMR studies and the absolute configuration was established by NOESY and CD spectra. Dysoline (1) consisted of a 5,7-dihydroxy-2-methylchromone nucleus substituted with a 2′-hydroxylated N-Me piperidine ring at the C-6 position. Dysoline differs from rohitukine by the position of the piperidine ring on the chromone nucleus. Dysoline displayed promising cytotoxicity in HT1080 fibrosarcoma cells with an IC₅₀ of 0.21 μM, and also displayed significant inhibition of proinflammatory cytokines TNF-α and IL-6.     

Synthesis of some new mesoionic heterocycles

The synthesis of various substituted 1-hydroxy-2-chloroacetyl-6-thia-10b-aza-2a-azoniaaceanthrylene hydroxide inner salt, 1-hydroxy-6-thia-10b-aza-2a-azoniaaceanthrylene hydroxide inner salt, 1-hydroxy-2-piperidinoacetyl-6-thia-10b-aza-2a-azoniaaceanthrylene hydroxide inner salt is described. The ir is also included.     

Prenylated indole alkaloids and chromone derivatives from the fungus Penicillium sp. SCSIO041218

Four new prenylated indole alkaloids (1–4), and four new chromone derivatives (7–10), together with six known compounds (5, 6, and 11–14), have been isolated from the mangrove sediment derived fungus Penicillium sp. SCSIO041218, cultured in the 1% NaCl PDB substrate. The structures of new compounds were determined by analysis of the NMR and MS spectroscopic data. The absolute configuration of the prenylated indole alkaloids were elucidated based on the comparison of ECDs with known analogues. The absolute configurations of the chromone derivatives were determined by time-dependent density functional theory calculations of the ECD spectra. In all of these isolated compounds, penixanthones A and B (12 and 13) exhibited antiallergic activities in vitro.     

Synthesis of novel heterocycles from thiazolecarbohydrazides

Cyclization of 2-methyl (or -phenyl)-5-phenylthiazole-4-carbohydrazides (1) and (2) under various conditions gives differing oxadiazoles: 2-(2-substituted-5-phenyl-4-thiazolyl)-1,3,4-oxadiazole-5-thiones (7) and (8), and 2-(2-substituted-5-phenyl-4-thiazolyl)-1,3,4-oxadiazoles (9) and (10). Cyclodehydration of thiazolecarbonyl-thiosemicarbazides (3)–(6) with NaOH givesthe 3-(2-substituted-5-phenyl-4-thiazolyl)-4-substituted-4H-5-mercapto-1,2,4-triazoles (11)–(14), while H ₃ PO ₄ gives the 2-(2-substituted-5-phenyl-4-thiazolyl)-5-phenylamino-1,3,4-thiadiazoles (15) and (16).A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Science Center, Russian Academy of Sciences, 420083 Kazan'. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 3, pp. 679–683, March, 1992.