Indandione Derivatives Research Articles

Novel candidates synthesis of indenopyrazole, indenoazine and indenothiophene, with anticancer and in silico studies.

Aim: The indandione nucleus, is one of the most amazing nuclei in medicinal chemistry,is used to design new derivatives.Methods & materials: Novel indandione derivatives are prepared with different electrophilic and nucleophilic reagents to yield 3, 4, 8, 11, 14, 16, 19, 20, 21, 22 and 23. Compounds 8, 11, 16, 20 and 23 are investigated against OVCAR-3 and HeLa, using LLC-MK2 and cis-Pt as references. in silico and spectral studies were analyzed for the selected compounds.Results: Compounds 20 and 23 at 100ns were the most potent compounds, so molecular dynamics studies were performed.Conclusion: Compound 23 was the most active toward the HeLa cervical cell line, and compound 20 was the most active toward the Ovcar-3 cell line.

Effects of Electron-Withdrawing and Electron-Donating Groups on Aromaticity in Cyclic Conjugated Polyenes.

Determining the aromaticity of various fluorinated benzenes is challenging as easily obtained experimental aromaticity [Δδ(Houter - Hinner)] necessitates the chemical shifts of inner and outer protons. This issue was addressed in porphyrinoids by replacing the electron-withdrawing (E.W.) groups at the meso-positions of porphyrins and allyliporphyrins. Electronic effects on aromaticity in porphyrinoids have not been thoroughly examined in the literature. In porphyrins, the effect of E.W. groups is minimal, making it difficult to establish a clear relationship between the aromaticity strength and E.W. groups. Conversely, in allyliporphyrins, stronger E.W. groups, such as indandione (IND) derivatives, significantly reduce the aromaticity of the parent structure. The IND derivatives disrupted the aromatic pathway of allyliporphyrin more effectively than those attached to porphyrins. This is attributed to the absence of β-carbons in allyliporphyrins. The effect of electron-donating (E.D.) groups on porphyrins and allyliporphyrins was further investigated. Contrary to the initial assumption that the E.D. groups might enhance aromaticity owing to their ability to increase electron density, as the strength of the E.D. groups increased, the aromaticity of the porphyrinoids decreased. Despite the modest reduction in aromaticity, any form of electron perturbation reduces aromaticity. The aromaticity of various fluorinated benzenes is expected to parallel our observations of porphyrinoids as representative aromatic polyenes.

Novel conjugated polymers based on cyclopenta[c]thiophene-4,6(5H)-dione for efficient polymer solar cells

A series of polymers based on indandione derivatives, TIND-HT-BDT, TIND-HT-BDTF, TIND-DHT-BDT, and TIND-DHT-BDTF, were synthesized as donor materials for polymer solar cells (PSCs). The polymers have a typical donor-acceptor configuration, where TIND-HT (5-((5-hexylthiophen-2-yl)methylene)-4H-cyclopenta[c]thiophene-4,6(5H)-dione) and TIND-DHT (5-((4,5-dihexylthiophen-2-yl)methylene)-4H-cyclopenta[c]thiophene-4,6(5H)-dione) are the electron acceptor units, while benzodithiophene (BDT) or fluorinated benzodithiophene (BDTF) are the electron donor units. Non-fullerene inverted-type PSCs with a configuration of ITO/ZnO/polymer:Y6BO/MoO3/Ag devices based on polymers as the donor and Y6BO as the acceptor were fabricated. The best power conversion efficiency (PCE) of 11.1% was achieved using the inverted-type PSCs based on TIND-DHT-BDTF with an open-circuit voltage (Voc) of 0.82 V and short-circuit current density (Jsc) of 22.6 mA/cm2. This study provides insights into novel donor materials for non-fullerene PSCs.

D-π-A type conjugated indandione derivatives: ultrafast broadband nonlinear absorption responses and transient dynamics.

The ultrafast nonlinear optical response of two 1,3-indandione derivatives (INB3 and INT3) was systematically investigated by the femtosecond Z-scan and pump-probe technique at multiple visible and near infrared wavelengths. Both compounds show strong broadband nonlinear absorption (NLA) and different wavelength-dependent two-photon absorption (TPA) characteristics in the range of 650–1100 nm. The TPA cross section of trithiophene-based compound INT3 was found to be larger than that of triphenylamine-based compound INB3 in the red region (650–800 nm), which is attributed to its longer π-conjugated structure and better molecular planarity. Interestingly, the effective NLA of INB3 was found to be larger than INT3 in the NIR region (800–1100 nm), which is related to the excited state absorption (ESA) induced by TPA. The ultrafast dynamics of both compounds were investigated by femtosecond transient absorption spectroscopy, which revealed a broadband ESA including several relaxation processes. This work extends nonlinear optical research on indandione derivatives, and the results suggest that these derivatives are promising candidates for optical limiting applications.

Leishmanicidal and cytotoxic activities and 4D-QSAR of 2-arylidene indan-1,3-diones.

The indan-1,3-dione and its derivatives are important building blocks in organic synthesis and present important biological activities. Herein, the leishmanicidal and cytotoxicity evaluation of 16 2-arylidene indan-1,3-diones is described. The compounds were evaluated against the leukemia cell lines HL60 and Nalm6, and the most effective ones were 2-(4-nitrobenzylidene)-1H-indene-1,3(2H)-dione (4) and 4-[(1,3-dioxo-1H-inden-2(3H)-ylidene)methyl]benzonitrile (10), presenting IC50 values of around 30 µmol/L against Nalm6. The leishmanicidal activity was assessed on Leishmania amazonensis, with derivative 4 (IC50 = 16.6 µmol/L) being the most active. A four-dimensional quantitative structure-activity analysis (4D-QSAR) was applied to the indandione derivatives, through partial least-squares regression. The statistics presented by the regression models built with the selected field descriptors of Coulomb (C) and Lennard-Jones (L) nature, considering the activities against L. amazonensis, HL60, and Nalm6 leukemia cells, were, respectively, R2 = 0.88, 0.92, and 0.98; Q2 = 0.83, 0.88, and 0.97. The presence of positive Coulomb descriptors near the carbonyl groups indicates that these polar groups are related to the activities. Besides, the presence of positive Lennard-Jones descriptors close to substituents R3 or R1 indicates that bulky nonpolar substituents in these positions tend to increase the activities. This study provides useful insights into the mode of action of indandione derivatives for each biological activity involved.

Indandione and Its Derivatives - Chemical Compounds with High Biological Potential.

Indandione is a hydrocarbon classified as bicyclic aromatic β-diketone. It can be applied in many fields of science and industry. It is successfully used as a substrate in organic synthesis, pharmaceutical sciences and as a substrate for the production of dyes. Indandione derivatives and analogs are useful in medicine, chemistry and the judiciary. Among the indandione derivatives can find compounds that have interesting properties and many of them have biological activity (incl. anticancer, anticoagulation, anti-inflamatory, antimicrobial activities). Based on the indan-1,3-dione structure created acetylcholinesterase inhibitors. Indan-1,3-dione derivatives are also used as a derivating agent for the analysis of fatty aldehydes and a substance that is an element of dye-sensitized solar cells. This work presents a brief overview of construction, properties and activities of indandione and its derivatives. This work describes selected indandione derivatives that have properties useful in medicine and industry with particular regard to the anticoagulants and neuroprotective activities in AD.

Study of Structure–Third-Order Susceptibility Relation of Indandione Derivatives

By using the Z-scan method we studied the third-order nonlinear optical parameters of several aminobenziliden-1,3-indandione (ABI) derivatives that have previously been shown to own second-order nonlinear optical properties. Measurements were carried out using two 1064 nm Nd:YAG lasers with picosecond (ps) and nanosecond (ns) pulse widths, respectively. When ns laser was employed in the Z-scan setup, a strong thermal lensing took place resulting in severe overestimation of optical Kerr coefficients. Due to this reason the ps laser was employed to evaluate correct magnitude of Kerr effect. For investigated organic molecules, experimental results show that two-photon absorption at 1064 nm is in correlation with molar extinction coefficient at 532 nm. Here we demonstrate good linear correlation between values of second-order molecular hyperpolarizability determined experimentally and those obtained by quantum chemical modeling.

Design, synthesis and evaluation of novel indandione derivatives as multifunctional agents with cholinesterase inhibition, anti-β-amyloid aggregation, antioxidant and neuroprotection properties against Alzheimer’s disease

A series of novel 2-(4-(4-substituted piperazin-1-yl)benzylidene)-1H-indene-1,3(2H)-diones were designed, synthesized and appraised as multifunctional anti-Alzheimer agents. In vitro studies of compounds 27–38 showed that these compounds exhibit moderate to excellent AChE, BuChE and Aβ aggregation inhibitory activity. Notably, compounds 34 and 38 appeared as most active multifunctional agents in the entire series and exhibited excellent inhibition against AChE (IC50=0.048μM: 34; 0.036μM: 38), Aβ aggregation (max% inhibition 82.2%, IC50=9.2μM: 34; max% inhibition 80.9%, IC50=10.11μM: 38) and displayed significant antioxidant potential in ORAC-FL assay. Both compounds also successfully diminished H2O2 induced oxidative stress in SH-SY5Y cells. Fascinatingly, compounds 34 and 38 showed admirable neuroprotective effects against H2O2 and Aβ induced toxicity in SH-SY5Y cells. Additionally, both derivatives showed no considerable toxicity in neuronal cell viability assay and represented drug likeness properties in the primarily pharmacokinetics study. All these results together, propelled out that compounds 34 and 38 might serve as promising multi-functional lead candidates for treatment of AD in the future.

Relation between molecule ionization energy, film thickness and morphology of two indandione derivatives thin films

Nowadays most organic devices consist of thin (below 100nm) layers. Information about the morphology and energy levels of thin films at such thickness is essential for the high efficiency devices. In this work we have investigated thin films of 2-(4-[N,N-dimethylamino]-benzylidene)-indene-1,3-dione (DMABI) and 2-(4-(bis(2-(trityloxy)ethyl)amino)benzylidene)-2H-indene-1,3-dione (DMABI-6Ph). DMABI-6Ph is the same DMABI molecule with attached bulky groups which assist formation of amorphous films from solutions. Polycrystalline structure was obtained for the DMABI thin films prepared by thermal evaporation in vacuum and amorphous structure for the DMABI-6Ph films prepared by spin-coating method. Images taken by SEM showed separate crystals or islands at the thickness of the samples below 100nm. The ionization energy of the studied compounds was determined using photoemission yield spectroscopy. A vacuum level shift of 0.40eV was observed when ITO electrode was covered with the thin film of the organic compound. Despite of the same active part of the investigated molecules the ITO/DMABI interface is blocking electrons while ITO/DMABI-6Ph interface is blocking holes.

Inhibition of the HIF1α-p300 interaction by quinone- and indandione-mediated ejection of structural Zn(II)

Protein–protein interactions between the hypoxia inducible factor (HIF) and the transcriptional coactivators p300/CBP are potential cancer targets due to their role in the hypoxic response. A natural product based screen led to the identification of indandione and benzoquinone derivatives that reduce the tight interaction between a HIF-1α fragment and the CH1 domain of p300. The indandione derivatives were shown to fragment to give ninhydrin, which was identified as the active species. Both the naphthoquinones and ninhydrin were observed to induce Zn(II) ejection from p300 and the catalytic domain of the histone demethylase KDM4A. Together with previous reports on the effects of related compounds on HIF-1α and other systems, the results suggest that care should be taken in interpreting biological results obtained with highly electrophilic/thiol modifying compounds.

Assembl y of Poly-3-Hexylthiophene Nano-Crystallites into Low Dimensional Structures Using Indandione Derivatives.

Conductive polymer poly-3-hexylthiophene (P3HT) needles were self-assembled using a second component (indandione derivatives) as a linking agent to enhance their long range alignment. The morphologies of the hybrid organic/organic materials were characterized by transmission electron microscopy (TEM). Both linear and branched structures could be produced, with the degree of branching depending upon the linker used. Incorporation of indandione derivatives broadened the UV absorbance band of P3HT without significant change to its photoluminescence. This hybrid material could open a promising avenue in photovoltaic applications due to its interesting morphologies and optical properties.

Electrochemical synthesis of novel 1,3-indandione derivatives and evaluation of their antiplatelet aggregation activities.

Electrochemical oxidation of some selected catechol derivatives, using cyclic voltammetry, in the presence of different 2-aryl-1,3-indandiones as nucleophiles, resulted in electrochemical synthesis of new 1,3- indandione derivatives in an undivided cell in good yield and purity. A Michael addition mechanism was proposed for the formation of the analogs based on the reaction conditions which were provided in electrochemical cell. The in-vitro antiplatelet and anticoagulant activity of these compounds was evaluated, using arachidonic acid (AA) and adenosine diphosphate (ADP) as the platelet aggregation inducers. The results show that the incorporation of catechol ring in 1,3-indandione nucleus leads to the emergence of antiplatelet aggregation activity in these compounds. The compounds may exert their antiaggregation activity by interfering with the arachidonic acid pathway.

Potentiometric determination of ionisation constants for diphacinone and chlorophacinone in a dioxane–water cosolvent system

The purpose of this study was to determine the ionisation constants of two poorly soluble compounds, namely diphacinone and chlorophacinone, potentiometrically in 1,4-dioxane–water mixtures with ibuprofen used as a standard. In this study, Gran's method was employed for the calibration of glass electrode in cosolvent systems with pH measurements based on the concentration scale (p cH). Aqueous p K a values for the tested compounds were obtained by extrapolation on a Yasuda–Shedlovsky plot. It was demonstrated that the p K a for ibuprofen determined using this method was consistent with those reported in literature. The technique was applied successfully to the two indandione derivatives, diphacinone and chlorophacinone. The present study demonstrated that the use of an organic cosolvent is effective in improving the solubility of compounds allowing potentiometric determination of ionisation constants that are otherwise difficult in aqueous solutions.

Polymers films with indandione derivatives as alternatives to azobenzene polymers for optical patterning

Surface relief gratings (SRGs) on organic thin films are studied extensively for both scientific interest and in relevance to the applications. Among the chromophores being used the azobenzenes showed the best performance, but the use of alternative photo-sensitive groups provides better general understanding of the phenomena. A thermodynamic theory and molecular dynamics simulations of photoinduced effects are discussed. In this study we use indandione derivatives, known as promising materials for photonics applications, as an alternative to the azobenzenes. We consider their photoreactions when incorporated into a polymer film. One of interesting features is the spectral dependence of the diffraction of indandione containing gratings, which is observed and discussed.

2-D effects in the second-order optical nonlinearity of organic molecules incorporating carbazole

The second order nonlinearity ( β) of a series of organic π-conjugated molecules involving 1,3 indandione derivatives as an acceptor moiety has been measured. The effect of varying the donor from dialkylamino to N-carbazolyl substituents was examined. Despite the chemically similar nature of the two donors, a drastic reduction of electric field induced second harmonic (EFISH) β values for the molecules involving the N-carbazolyl substituents was detected. Quantum mechanical calculations indicate that the decrease in β values results from the presence of two overlapping transitions that contribute to β with opposite signs. Thus, the charge transfer band gives a positive β zzz contribution along the long molecular axis, while a transition essentially within the carbazole group provides a negative β zxx contribution to β EFISH. Therefore, these molecules can only be described with a two-dimensional model as opposed to the ‘classical’ one-dimensional model for NLO chromophores. Experimental verification of this hypothesis was provided by a combination of two experimental methods, EFISH and hyper Rayleigh scattering (HRS). Each technique probes a different combination of the β tensor elements, so we could deduce the two contributions.

Synthesis of potential antineoplastics by condensation of phthalic anhydride with 4-bis(2-chloroethyl)aminophenylacetic acid

Indandione, its enol acetate, and the products of a parallel reaction — a mixture of isomeric acidsE, Z-5, and phthalide — are formed in the reaction of substituted phenylacetic acid with phthalic anhydride in acetic anhydride and triethylamine. 2-Substituted indandione derivatives were obtained.

Drug Therapy Review—Coumarin and Indandione Derivatives

Journal Article Drug Therapy Review—Coumarin and Indandione Derivatives Get access American Journal of Hospital Pharmacy, Volume 30, Issue 8, 1 August 1973, Pages 705–713, https://doi.org/10.1093/ajhp/30.8.705 Published: 01 August 1973

Photoelectrical Properties and Energetical Structure of Thin Films of Indandione Derivatives

A sandwich type structure of two dimetilaminobenziliden-1,3-indandione (DMABI) derivatives placed between metal electrodes was made to investigate the photoelectrical properties of these derivatives. DMABI is an organic isolator with a wide energy gap and high quantum efficiency of the photogeneration, DMABI derivatives have received also considerable attention because of its large dipole moment and optical nonlinearities. Besides, since it is a photosensitive material, its use in solar systems is very promising. The energy gap of each material and combined system was observed from the spectral dependence of the quantum efficiency of the photoconductivity and results are compared with results of oxidation and reduction potential of the materials. The values showed a good correlation between experimental data of the photoconductivity and voltamperometry and calculated data of the HOMO and LUMO levels of the molecules.http://dx.doi.org/10.5755/j01.ms.17.2.480

EFFECT OF ORAL ANTICOAGULANTS ON FACTORS VII, IX, X, AND II.

In THE MORE than two decades since Campbell and Link¹isolated bishydroxycoumarin as the hemorrhagic agent in spoiled sweet clover, numerous other coumarins and the related indandione derivatives have been developed and widely used as anticoagulants.²Studies of the effect of these oral anticoagulants on blood coagulation have indicated that most of these drugs depress not only prothrombin,³but three other clotting activities as well—factors VII,⁴IX,⁵and X⁶—although evidence has been presented^7,8that certain anticoagulant drugs differ qualitatively in their effect on the clotting mechanism. Furthermore, despite numerous isolated studies on individual drugs, the exact sequence in which the levels of various affected clotting factors decrease with coumarin or indandione therapy is not a matter of general agreement.⁹A systematic study of the effect of commonly used coumarin and indandione drugs using specific assays for each of the four coagulation factors were the same as those usually observed during

Concerning the analgesic and anticonvulsive activity of some anticoagulant drugs and vitamin K

Summary The analgesic properties of vitamin K, 4-hydroxycoumarine and some coumarine and indandione derivatives were studied. The analgesic effectiveness of 4-hydroxycoumarine was not affirmed; vitamin K, warfarine and the bromo and nitro-derivatives of a-naphthylindandione were effective only by using the method with radiant heat. Some of derivatives of α- and β-naphtylindandione exerted a protective effect against electroschock in mice, but no dependence on their anticoagulative action was found.