Synthesis and Cytotoxicity Evaluation of Metal‐Chelator‐Bearing Flavone,Carbazole, Dibenzofuran,Xanthone, and Anthraquinone

2‐(Aryloxymethyl)‐5‐benzyloxy‐1‐methyl‐1H‐pyridin‐4‐ones 8a – 8g , 2‐(aryloxymethyl)‐5‐hydroxy‐4H‐pyran‐4‐ones 9a – 9g , and 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were prepared from the known 5‐benzyloxy‐2‐(hydroxymethyl)pyran‐4‐one ( 3 ) in a good overall yield. These compounds were evaluated in vitro against a three‐cell lines panel consisting of MCF7 (breast), NCI‐H460 (lung), and SF‐268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5‐hydroxy derivatives are more favorable than their corresponding 5‐benzyloxy precursors ( 10a – 10g vs. 8a – 8g ), and 1‐methyl‐1H‐pyridin‐4‐ones are more favorable than their corresponding pyran‐4(1H)‐ones ( 10a – 10g vs. 9a – 9g ). Among these three types of compounds, 2‐(aryloxymethyl)‐5‐hydroxy‐1‐methyl‐1H‐pyridin‐4‐ones 10a – 10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI₅₀=27.8 μM ), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK‐MEL‐5 (a melanoma cancer cell) with a GI₅₀ of <0.01, 5.65, 0.55, and 0.03 μM , respectively (cf. Table 2).     

Synthesis and Cytotoxicity Evaluation of Certain α‐Methylidene‐ γ‐butyrolactones Bearing Coumarin,Flavone, Xanthone,Carbazole, and Dibenzofuran Moieties

The cytotoxicities of α‐methylidene‐γ‐butyrolactones, which are linked to coumarins (see 15 and 16 ) and to potential DNA‐intercalating carriers such as flavones, xanthones, carbazole, and dibenzofuran (see 9a – e , 10a – e , 11 , and 12 ), were studied. These compounds were synthesized via alkylation of their hydroxy precursors followed by a Reformatsky‐type condensation (Scheme). These α‐methylidene‐γ‐butyralactones were evaluated in vitro against 60 human tumor cell lines derived from nine cancer cell types and demonstrated a strong growth‐inhibitory activity against leukemia cancer cells (Tables 1 and 2). For flavone‐ and xanthone‐containing α‐methylidene‐γ‐butyrolactones 9a – e and 10a – e , respectively, the overall potency (mean value) decreased on introduction of an electron‐withdrawing substituent at the γ‐phenyl substituent and increased with an electron‐donating substituent. Comparing the different chromophores established the following order of decreasing potency (log GI₅₀): dibenzofuran ( 12 , −6.17) > flavone ( 9a , −5.96) > carbazole ( 11 , −5.80) and xanthone ( 10a , −5.77) > coumarin ( 15 , −5.60; 16 , −5.65). Among them, the dibenzofuran derivative 12 showed not only strong inhibitory activities against leukemia cancer cell lines with an average log GI₅₀ value of −7.22, but also good inhibitory activities against colon, melanoma, and breast cancer cells with average log GI₅₀ values of −6.23, −6.31, and −6.39, respectively.     

Synthesis,Cytotoxic Activity Evaluation of Novel 1,2,3‐Triazole Linked Quinazoline Derivatives

A series of novel 1,2,3‐triazole‐quinazoline derivatives were synthesized in five steps starting from anthranilamide by conventional methods. All the title compounds 10a — 10r were evaluated for cytotoxic activity against four human cancer cell lines (MGC ‐803, EC ‐109, MCF ‐7 and HGC ‐27) using MTT assay in vitro . Some of the synthesized compounds exhibited moderate to potent activity against tested cancer cell lines. Among them, compounds 10 h and 10q exhibited excellent growth inhibition against HGC ‐27 and compound 10 m also possessed excellent activity against MCF ‐7, with IC₅₀ values less than 1 µmol/L. Especially, compound 10 h was more cytotoxic than 5‐fluorouracil against all tested four human cancer cell lines.     

Synthesis and Cytotoxic Evaluation of Novel 1,2,3‐Triazole‐4‐Linked (2E,6E)‐2‐Benzylidene‐6‐(4‐nitrobenzylidene)cyclohexanones

This work describes the synthesis of novel 1,2,3‐triazole‐4‐linked (2E,6E)‐2‐benzylidene‐6‐(4‐nitrobenzylidene)cyclo‐hexanones starting from cyclohexanone. 1‐(Cyclohex‐1‐en‐1‐yl)piperidine, the enamine from cyclohexanone and piperidine, reacted with 4‐nitrobenzaldehyde to obtain 2‐(4‐nitrobenzylidene)cyclohexanone. Condensation of the latter compound with (prop‐2‐yn‐1‐yloxy)benzaldehyde derivatives under acidic conditions gave (4‐nitrobenzylidene)‐[(prop‐2‐yn‐1‐yloxy)‐benzylidene]cyclohexanones. Finally, ‘click reaction’ of these derivatives and various organic azides led to the title compounds. All compounds were examined by MTT assay for cytotoxic activity in one human breast cancer cell line, MDA‐MB‐231.     

Synthesis and Pharmacological Evaluation of 4‐Aryloxyquinazoline Derivatives as Potential Cytotoxic Agents

In the present study, novel 4‐aryloxyquinazoline derivatives were synthesized and screened for in vitro cytotoxicity on human cancer cell lines at 10 μM. Some of the synthesized compounds displayed moderate to significant and selective cytotoxic activity against various leukemia, melanoma, ovarian, breast, and colon cancer cell lines. (E)‐3‐(3,4‐Dimethoxyphenyl)‐1‐(4‐(quinazolin‐4‐yloxy)phenyl)prop‐2‐en‐1‐one ( 9b ) was the most potent compound among all with an average growth inhibition of 70% against leukemia cancer cell lines. The compound also produced strong inhibition (75%) of colon cancer cell lines with 42.58% lethality of HCT‐116 cell line.     

Synthesis,Characterization, and In Vitro Antimicrobial Activity of Methyleneamine‐Linked Bis‐heterocycles

A new class of methyleneamine‐linked bis‐heterocycles that exhibit antimicrobial activity was synthesized. Bromination of 1 followed by condensation with thiourea gave 3 . The reaction of 3 with propargyl bromide in dry toluene under inert atmosphere led to the formation of 4 . Its subsequent reaction with different nitrile oxides using CuSO₄.5H₂O–sodiumascorbate system in a 2:1 mixture of water and tert‐butyl alcohol yielded the title compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k , 6l in good yields. The identities of these compounds were confirmed following elemental analysis, IR, ¹H, ¹³C NMR, and mass spectral studies. All the title compounds exhibited pronounced in vitro antibacterial and antifungal activities.     

Luminescent Polymer Consisting of 9,12‐Linked o‐Carborane

The synthesis of novel luminescent polymer containing p‐phenylene‐ethynylene and 9,12‐linked o‐carborane units alternately in the main chain is reported. The obtained polymer exhibits intense blue photoluminescence, providing the first insights into the optical properties of a 9,12‐disubstituted o‐carborane dye.  π‐Conjugated substituent at 9 and/or 12‐positions in o‐carborane is electrically independent, and both the HOMO and the LUMO levels slightly increase, whereas LUMO of the π‐conjugated substituent at 1 and/or 2‐positions in o‐carborane decrease.  Thus, it is deduced that polymers consisting of the 9,12‐linked o‐carborane unit are able to be applied as light‐emitting materials.

     

Synthesis of Bis‐ and Tris(3‐H‐1,3‐azaphospholo)benzenes

The previously developed intramolecular cyclocondensation of C‐phosphanyl(N‐aryl)formamidines into 3‐H‐1,3‐benzazaphospholes has been successfully extended to 1,3‐diaminobenzene and 1,3,5‐triaminobenzene. Its condensation presents the way to tricyclic and tetracyclic azaphospholes. Their structures were confirmed by spectroscopic methods and key tricyclic and tetracyclic compounds were further characterized by single crystal X‐ray diffraction.     

New Bis(dihydropyridine‐3,5‐dicarbonitrile) Derivatives: Green Synthesis and Cytotoxic Activity Evaluation

A synthesis of bis(dihydropyridine‐3,5‐dicarbonitrile) by a three‐component reaction of one equivalent of bis‐cyanoacetamides with two equivalents of both arylaldehydes and malononitrile in ethanol‐containing piperidine is reported. Bis‐cyanopyridones could also be obtained by the condensation of bis‐cyanoacetamides with substituted arylidenemalononitriles in the presence of piperidine, chitosan, or montmorillonite as basic catalysts. The cytotoxicity of the synthesized products against the heterogeneous human epithelial colorectal adenocarcinoma cell line (Caco‐2) was assessed by WST‐1 assay with concentration dependent cellular growth inhibitory effect especially for compounds 5l , 5h , and 5d . The dose response curves indicate that IC50 were 87 ± 3.11 μg/mL, 104 ± 4.78 μg/mL, and 108 ± 5.12 μg/mL, respectively.     

Novel Disubstituted Phenylene‐Linked Bis‐imidazole Derivatives: Facile Synthesis and Optical Properties

Six novel disubstituted phenylene‐linked bis‐imidazole derivatives, 3a – 3f , were prepared by a one‐pot, microwave‐assisted method under solvent‐free conditions, in yields ranging from 61.6 to 85.6%. The new compounds were characterized by ¹H‐ and ¹³C‐NMR, UV/VIS, and fluorescence spectroscopy, and mass spectrometry, as well as by elemental analyses. The influence of substituents and solvents on the optical properties of 3a – 3f was investigated. It was found that there is little influence on absorption and excitation spectra in contrast to emission spectra. Compounds 3a – 3f exhibit strong fluorescence in solution, their fluorescence quantum yields ranging from 0.27 to 0.96.     

Synthesis and Supramolecular Assemblies of Tripodal 1,3,5‐Tris(phenoxymethyl)‐2,4,6‐triethylbenzene Analogues

Tripodal 1,3,5‐tris(phenoxymethyl)‐2,4,6‐triethylbenzene analogues have been synthesized and structurally characterized by IR, ¹H NMR and ¹³C NMR spectroscopy and HRMS, and additionally, the single crystal structures of compounds bearing ortho‐ ( 7 ), meta‐ ( 9 ) and para‐hydroxymethyl ( 11 ) functions have been determined by X‐ray diffraction analysis. The structural study revealed that compounds 7 , 9 , and 11 do not adopt the expected 1,3,5‐alternate conformation in the solid state. The packing diagrams of compounds 7 , 9 , and 11 revealed that six hydrophilic hydroxymethyl groups from six individual molecules ( 7 , 9 and 11 ) were arranged in close contact via intermolecular hydrogen‐bond interactions. For compounds 7 and 9 , the six hydroxyl groups formed a distorted hexagonal ring; however, formation of such a hexagonal ring was not clear in the case of compound 11 . Compounds 9 and 11 were found to form hydrophobic cavities via intermolecular hydrogen‐bond interactions in the solid state, and the cavities were occupied by two ethyl groups from the two cavity‐forming molecules.     

A Novel Synthesis of Bis-（1,2,4-triazolyl）-3-disulfides

Manganese triacetate was introduced as a new reagent for radical cyclization of substituted aminothioureas. Bis-（1,2,4-triazolyl）-3-disulfides were generated in 10 min under microwave irradiation.     

Synthesis of 2(5H)‐Furanone Derivatives with Bis‐1,2,3‐triazole Structure

A series of new chiral 2(5H)‐furanone derivatives containing bis‐1,2,3‐triazole moiety were designed and synthesized from (5S)‐5‐alkoxy‐3,4‐dihalo‐2(5H)‐furanones 1 , dicarboxyl amino acids 2 , propargyl bromide, and organic azides 5 under mild conditions via the sequential three steps, including asymmetric Michael addition‐elimination, substitution and no‐ligand click reaction. Twelve new intermediates, including N‐[5‐alkoxy‐2(5H)‐furanonyl] dicarboxyl amino acids 3 and their corresponding propargyl esters 4 , and twelve target molecules 6 were characterized by FTIR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The influences of different synthetic conditions and substrates in each step were investigated. The research provides a new method and idea for the synthesis of 2(5H)‐furanone compounds with polyheterocyclic structure due to the diversities of four basic unit molecules.     

Synthesis,Characterization and Photophysical Properties of Iridium(III) Bis‐cyclometallated Complexes Containing 1,1‐Dithiolates

A series of neutral Ir(III)‐based heteroleptic complexes with a formula of [Ir(η²‐(C^∧N))₂(η²‐(S^∧S))] ((C^∧N)^‐ = ppy^‐, (S^∧S)^‐ = Et₂NCS₂^‐ ( 2a ), MeOCS₂^‐ ( 2b ), EtOCS₂^‐ ( 2c ), ⁱPrOCS₂^‐ ( 2d ); (C^∧N)^‐ = tpy^‐, (S^∧S) = Et₂NCS₂^‐ ( 3a ), MeOCS₂^‐ ( 3b ), EtOCS₂^‐ ( 3c ), ⁱPrOCS₂^‐ ( 3d ); (C^∧N)^‐ = epb^‐ , (S^∧S)^‐ = Et₂NCS₂^‐ ( 4a ), MeOCS₂^‐ ( 4a ), EtOCS₂^‐ ( 4a ); ppyH = 2‐phenylpyridine; tpyH = 2‐(4′‐tolyl)pyridine; epbH = ethyl 4‐(2′‐pyridyl)benzate) was synthesized and characterized. The crystal structure of complex 2d was also determined. The electron‐releasing substituents on (C^∧N)^‐ or (S^∧S)^‐ blueshift λ_max values.     

Synthesis,Cytotoxic Evaluation,and In Silico Studies of 4‐Substituted Coumarins

Two series of coumarins possessing the aniline‐ and heterocyclic ring at 4^th position have been synthesized and evaluated for their in vitro cytotoxic activity against MCF‐7 cancer cell line in MTT assay. Structure activity relationship (SAR) studies reveal that the electron donor group at position‐8 of coumarin played an important role in cytotoxic activity. Compound VIId showed the potent cytotoxic activity followed by compound Xa with IC₅₀ = 6.25 and 6.50 μM, respectively. A docking study has also been carried out for the most potent compound to get an insight into molecular interactions with p50 subunit of NF‐κB protein.     

Synthesis of A New Compound: Octaiodo‐9,10‐Anthraquinone

A new compound: octaiodoanthraquinone (9,10) was synthesized from anthracene by a periodination process under the catalysis of mercury ions at 200?250 °C. This new compound was also synthesized from anthraquinone (9,10) via a similar process, which verified the mercury‐catalyzed mechanism involved in the synthesis of octaiodoanthraquinone (9,10) from anthracene.     

5,20‐Bis(ethoxycarbonyl)‐Substituted Antiaromatic [28]Hexaphyrin and Its Bis‐NiII and Bis‐CuII Complexes

5,20‐Bis(ethoxycarbonyl)‐[28]hexaphyrin was synthesized by acid catalyzed cross‐condensation of meso‐diaryl‐substituted tripyrrane and ethyl 2‐oxoacetate followed by subsequent oxidation. This hexaphyrin was found to be a stable 28π‐antiaromatic compound with a dumbbell‐like conformation. Upon oxidization with PbO₂, this [28]hexaphyrin was converted into an aromatic [26]hexaphyrin with a rectangular shape bearing two ester groups at the edge side. The [28]hexaphyrin can incorporate two Ni^II or Cu^II metals by using the ester carbonyl groups and three pyrrolic nitrogen atoms to give bis‐Ni^II and bis‐Cu^II complexes with essentially the same dumbbell‐like structure. The antiaromatic properties of the [28]hexaphyrin and its metal complexes have been well characterized.     

Calix[4]arene‐based Bis‐phosphonites,Bis‐phosphites,and Bis‐O‐acyl‐phosphites as Ligands in the Rhodium(I)‐catalyzed Hydroformylation of 1‐Octene

New calix[4]arene‐based bis‐phosphonites, bis‐phosphites and bis‐O‐acylphosphites were synthesized and characterized. Treatment of these P‐ligands with selected rhodium and platinum precursors led to mononuclear complexes that were satisfactorily characterized. The solid state structure of the dirhodium(I) complex 14 has been determined by X‐ray diffraction. The two rhodium centres are bridged by two chloro ligands; one rhodium atom is further coordinated by calix[4]arene phosphorus atoms and the other by cyclooctadiene. The new calix[4]arene P‐ligands were tested in the Rh(I) catalyzed hydroformylation of 1‐octene. All Rh(I) complexes catalyzed the reaction leading to high chemoselectivity with regard to the formation of aldehydes. Yields and n/iso‐selectivities depended on the reaction conditions. Average yields of 80 % and n/iso‐ratios of about 1.3 to 1.5 were observed. High yields of aldehydes can be achieved using the methoxy substituted P‐ligands at low Rh:ligand ratios.