Naphthoquinone Moiety Research Articles

Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases

Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6–305 µM, MIC: 0.5–128 µg ml−1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity.

Synthesis, anti-inflammatory activity, inverse molecular docking, and acid dissociation constants of new naphthoquinone-thiazole hybrids

Chronic Inflammation is associated with various types of diseases that involves pro-inflammatory cytokines like IL-6 and TNF-α. High costs and serious side effects of available anti-inflammatory/immunomodulatory drugs led us to design new compounds with promising anti-inflammatory activities. Many drugs and biologically important compounds involve naphthoquinone and thiazole moieties in their core structures. Thereby, here we report the synthesis, characterization and anti-inflammatory activities of new naphthoquinone thiazole hybrids by reaction of naphthoquinone acyl thioureas with various α-bromoketone derivatives. The position of NO2 group in one of the phenyl rings of naphthoquinone thiazole hybrids was changed while different substituents were introduced at the para position of the second phenyl ring. All compounds were tested for potential immunomodulatory effect. No inflammatory cytokines were observed in the absence of LPS stimulant. On the other hand, they had promising anti-inflammatory immunomodulatory activities by being able to decrease the production of the pro-inflammatory cytokines (TNF-α and IL-6) in the LPS-stimulated cells. In an effort to find the possible mechanism of action, several enzymes involved in signalling pathways that play critical roles in inflammatory responses were screened in silico. Subsequent to inverse molecular docking approach, PI3K was predicted be the potential target. The docked complexes of the most potent compounds 5g and 5i were subjected to molecular dynamics simulation to assess the binding stability of the igands with the putative target. Acid dissociation constants (pKa) of the products were also determined potentiometrically.

Molecular Docking and Dynamics Simulation Studies Predict Potential Anti-ADAR2 Inhibitors: Implications for the Treatment of Cancer, Neurological, Immunological and Infectious Diseases.

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from -81.304 to -1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (-1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [-873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.

In vitro activity of rhinacanthin analogues against drug resistant Plasmodium falciparum isolates from Northeast Thailand

BackgroundNew anti-malarial drugs are needed urgently to address the increasing challenges of drug-resistant falciparum malaria. Two rhinacanthin analogues containing a naphthoquinone moiety resembling atovaquone showed promising in-vitro activity against a P. falciparum laboratory reference strain (K1). The anti-malarial activity of these 2 compounds was further evaluated for P. falciparum field isolates from an area of multi-drug resistance in Northeast Thailand.MethodsUsing a pLDH enzyme-linked immunosorbent assay, four P. falciparum isolates from Northeast Thailand in 2018 were tested for in vitro sensitivity to the two synthetic rhinacanthin analogues 1 and 2 as well as established anti-malarials. Mutations in the P. falciparum cytochrome b gene, a marker for atovaquone (ATQ) resistance, were genotyped in all four field isolates as well as 100 other clinical isolates from the same area using PCR-artificial Restriction Fragment Length Polymorphisms. Pfkelch13 mutations, a marker for artemisinin (ART) resistance, were also examined in all isolates.ResultsThe 50% inhibitory concentrations (IC50) of P. falciparum field isolates for rhinacanthin analogue 1 was 321.9–791.1 nM (median = 403.1 nM). Parasites were more sensitive to analogue 2: IC50 48.6–63.3 nM (median = 52.2 nM). Similar results were obtained against P. falciparum reference laboratory strains 3D7 and W2. The ART-resistant IPC-5202 laboratory strain was more sensitive to these compounds with a median IC50 45.9 and 3.3 nM for rhinacanthin analogues 1 and 2, respectively. The ATQ-resistant C2B laboratory strain showed high-grade resistance towards both compounds (IC50 > 15,000 nM), and there was a strong positive correlation between the IC50 values for these compounds and ATQ (r = 0.83–0.97, P < 0.001). There were no P. falciparum cytochrome b mutations observed in the field isolates, indicating that P. falciparum isolates from this area remained ATQ-sensitive. Pfkelch13 mutations and the ring-stage survival assay confirmed that most isolates were resistant to ART.ConclusionsTwo rhinacanthin analogues showed parasiticidal activity against multi-drug resistant P. falciparum isolates, although less potent than ATQ. Rhinacanthin analogue 2 was more potent than analogue 1, and can be a lead compound for further optimization as an anti-malarial in areas with multidrug resistance.

Hybrid Molecules Containing Naphthoquinone and Quinolinedione Scaffolds as Antineoplastic Agents.

In recent decades, molecular hybridization has proven to be an efficient tool for obtaining new synthetic molecules to treat different diseases. Based on the core idea of covalently combining at least two pharmacophore fragments present in different drugs and/or bioactive molecules, the new hybrids have shown advantages when compared with the compounds of origin. Hybridization could be successfully applied to anticancer drug discovery, where efforts are underway to develop novel therapeutics which are safer and more effective than those currently in use. Molecules presenting naphthoquinone moieties are involved in redox processes and in other molecular mechanisms affecting cancer cells. Naphthoquinones have been shown to inhibit cancer cell growth and are considered privileged structures and useful templates in the design of hybrids. The present work aims at summarizing the current knowledge on antitumor hybrids built using 1,4- and 1,2-naphthoquinone (present in natural compounds as lawsone, napabucasin, plumbagin, lapachol, α-lapachone, and β -lapachone), and the related quinolone- and isoquinolinedione scaffolds reported in the literature up to 2021. In detail, the design and synthetic approaches adopted to produce the reported compounds are highlighted, the structural fragments considered in hybridization and their biological activities are described, and the structure–activity relationships and the computational analyses applied are underlined.

Antioxidant, Antimicrobial, and Molecular Docking Studies of Novel Chalcones and Schiff Bases Bearing 1, 4-naphthoquinone Moiety

Background: The 1,4-naphthoquinone ring has attracted prominent interest in the field of medicinal chemistry due to its potent pharmacological activities such as antioxidant, antibacterial, antifungal, and anticancer. Objective: Herein, a series of new Schiff bases (4-6) and chalcones (8a-c &amp; 9a-d) bearing 1,4- naphthoquinone moiety were synthesized in good yields and were subjected to in-vitro antimicrobial, antioxidant, and molecular docking testing. Methods: A facile protocol has been described in this study for the synthesis of new derivatives (4-7, 8ac, and 9a-d) bearing 1,4-naphthoquinone moiety. The chemical structures of all the synthesized compounds were identified by 1H-NMR, 13C-NMR, MS, and elemental analyses. Moreover, these derivatives were assessed for their in-vitro antimicrobial activity against gram-positive, gram-negative bacteria, and fungal strains. Further studies were conducted to test their antioxidant activity using DPPH (2,2-diphenyl- 1-picrylhydrazyl) scavenging assay. Molecular docking studies were realized to identify the most likely interactions of the novel compounds within the protein receptor. Results: The antimicrobial results showed that most of the compounds displayed good efficacy against both bacterial and fungal strains. The antioxidant study revealed that compounds 9d, 9a, 9b, 8c, and 6 exhibited the highest radical scavenging activity. Docking studies of the most active antimicrobial compounds within GLN- 6-P, recorded good scores with several binding interactions with the active sites. Conclusion: Based on the obtained results, it was found that compounds 8b, 9b, and 9c displayed the highest activity against both bacterial and fungal strains. The obtained findings from the DPPH radical scavenging method revealed that compounds 9d and 9a exhibited the strongest scavenging potential. The molecular docking studies proved that the most active antimicrobial compounds 8b, 9b and 9c displayed the highest energy binding scores within the glucosamine-6-phosphate synthase (GlcN-6-P) active site.

Porphyrindiene-Based Tandem Diels–Alder Reaction for Preparing Low-Symmetry π-Extended Porphyrins with Push–Pull Skeletons

Tandem Diels-Alder reactions of masked porphyrindienes (i.e., sulfolenoporphyrins) with benzoquinones and stilbenes, followed by aromatization, have been developed to load porphyrin with mixed annulation units (i.e., terphenyl and naphthoquinone), furnishing the low-symmetry π-extended porphyrins (DxAy) with push-pull skeletons. All low-symmetrical chromophores display panchromatic absorption spectra, which look like a spectral combination of symmetrical congeners (D4/A4) in a certain ratio. Among them, tD2A2 with trans-arrangement of push/pull units possesses the largest maximum centered at 766 nm with the onset around 900 nm. The fusion of the electron-deficient naphthoquinone moiety on the porphyrin core results in the approximately quantitative regulation of the Eox1 and HOMOs (i.e., 0.10-0.13 V increase for the Eox1 and 0.14-0.16 eV decrease for the HOMOs per naphthoquinone unit). In brief, this work provides a new way to construct low-symmetry π-extended porphyrins with tunable properties resorting to the ratios and locations of the annulated push-pull units.

Synthesis and Antimalarial Activities of New Hybrid Atokel Molecules.

The currently spreading resistance of the malaria parasite Plasmodium falciparum to artemisinin‐based combination therapies makes an urgent need for new efficient drugs. Aiming to kill artemisinin‐resistant Plasmodium, a series of novel hybrid drugs named Atokels were synthesized and characterized. Atokels are based on an 8‐amino‐ or 8‐hydroxyquinoline entity covalently bound to a 1,4‐naphthoquinone through a polyamine linker. These drugs have been designed to target the parasite mitochondrion by their naphthoquinone moiety reminiscent of the antimalarial drug atovaquone, and to trigger a damaging oxidative stress due to their ability to chelate metal ions in order to generate redox active complexes in situ. The most effective Atokel drug shown a promising antimalarial activity (IC50=622 nm on an artemisinin‐resistant P. falciparum strain) and no cytotoxicity at 50 μm indicating a specific antiplasmodial mode of action.

Synthesis of novel acylthioureas bearing naphthoquinone moiety as dual sensor for high-performance naked-eye colorimetric and fluorescence detection of CN− and F− ions and its application in water and food samples

In this study, six new acylthiourea, bearing naphthoquinone moiety, sensors were synthesized in high yield (88–96%) and characterized using 1H/13C NMR, FT-IR and HRMS techniques. All synthesized sensors (4a-f) showed shifts in absorbance and colorimetric changes by CN−, F−, AcO−, and H2PO4−. However, 4e showed a chromogenic different sensitivity response to CN− and F− against competing anions such as AcO− and H2PO4− in DMSO. Furthermore, CN− added 4e showed an increase at the emission intensity and intensive fluorimetric color change was observed in UV-light (λex. 365 nm). All sensors showed chromogenic selectivity towards CN− in aqueous solutions (in DMSO/H2O: 1:1, v/v). Interaction mechanisms between 4e and CN− and F− anions were investigated by experimental studies using various spectroscopic methods such as UV/Vis, fluorescence, 1H/19F NMR, and DFT calculation. The results showed that CN− interacts with 4e by the main mechanism as nucleophilic addition of cyanide to 3,5-dinitrophenyl moiety while F− caused an occurrence of imidazole ring-closing due to deprotonation of NH2. LOD values are reported as 2.7 μM for sensor 4e. Moreover, interaction studies were carried out on food sample such as bitter almond, sprouting potato and apricot seed. Furthermore, UV/vis responses were obtained between sensors (4a-f) and the cations, and found selectivity towards Hg2+ in DMSO.

Anharmonicity and Spectra-Structure Correlations in MIR and NIR Spectra of Crystalline Menadione (Vitamin K3).

Mid-infrared (MIR) and near-infrared (NIR) spectra of crystalline menadione (vitamin K3) were measured and analyzed with aid of quantum chemical calculations. The calculations were carried out using the harmonic approach for the periodic model of crystal lattice and the anharmonic DVPT2 calculations applied for the single molecule model. The theoretical spectra accurately reconstructed the experimental ones permitting for reliable assignment of the MIR and NIR bands. For the first time, a detailed analysis of the NIR spectrum of a molecular system based on a naphthoquinone moiety was performed to elucidate the relationship between the chemical structure of menadione and the origin of the overtones and combination bands. In addition, the importance of these bands during interpretation of the MIR spectrum was demonstrated. The overtones and combination bands contribute to 46.4% of the total intensity of menadione in the range of 3600–2600 cm−1. Evidently, these bands play a key role in shaping of the C-H stretching region of MIR spectrum. We have shown also that the spectral regions without fundamentals may provide valuable structural information. For example, the theoretical calculations reliably reconstructed numerous overtones and combination bands in the 4000–3600 and 2800–1800 cm−1 ranges. These results, provide a comprehensive origin of the fundamentals, overtones and combination bands in the NIR and MIR spectra of menadione, and the relationship of these spectral features with the molecular structure.

Synthesis of styryl-linked fused dihydropyridines by catalyst-free multicomponent reactions.

Herein, we report a rapid catalyst-free three-component reaction of 2-hydroxy-1,4-naphthoquinone, cinnamaldehydes and 3-aminopyrazoles in ethanol medium under reflux conditions for the easy access of styryl-linked dihydropyridines fused with naphthoquinone and pyrazole moiety. A wide variety of cinnamaldehyde derivatives and 3-aminopyrazoles were found suitable for this three-component reaction. All the products were fully characterized by spectroscopic tools and by recording single crystal XRD of one of the product. Catalyst-free reaction conditions, short reaction time, good yields of the products, easy purification process, formation of three new bonds (Two C-C and one C-N) in one-pot and products having four different bioactive moieties are the notable features of this methodology.

Mitochondria-targeted dual-channel colorimetric and fluorescence chemosensor for detection of Sn2+ ions in aqueous solution based on aggregation-induced emission and its bioimaging applications

Several fluorescence and colorimetric chemosensory for Sn2+ detection in an aqueous media have been reported, but applications remain limited for discriminative Sn2+ detection in live human cells and zebrafish larvae. Herein, a mitochondria-targeted Sn2+ “turn-on” colorimetric and fluorescence chemosensor, 2CTA, with an aggregation-induced emission (AIE) response was developed. The sensing of Sn2+ was enabled by a reduction-enabled binding pathway, with the conversion of –C˭O groups to –C–OH groups at the naphthoquinone moiety. The color changed from light maroon to milky white in a buffered aqueous solution. The chemosensor 2CTA possessed the excellent characteristics of good water solubility, fast response (less than 10 s), and high sensitivity (79 nM) and selectivity for Sn2+ over other metal ions, amino acids, and peptides. The proposed binding mechanism was experimentally verified by means of FT-IR and NMR studies. The chemosensor 2CTA was successfully employed to recognize Sn2+ in live human cells and in zebrafish larvae. In addition, a colocalization study proved that the chemosensor had the ability to target mitochondria and overlapped almost completely with MitoTracker Red. Furthermore, a bioimaging study of live cells demonstrated the discriminative detection of Sn2+ in human cancer cells and the practical applications of 2CTA in biological systems.

Multi-Substrate Biofuel Cell Utilizing Glucose, Fructose and Sucrose as the Anode Fuels.

A significant problem still exists with the low power output and durability of the bioelectrochemical fuel cells. We constructed a fuel cell with an enzymatic cascade at the anode for efficient energy conversion. The construction involved fabrication of the flow-through cell by three-dimensional printing. Gold nanoparticles with covalently bound naphthoquinone moieties deposited on cellulose/polypyrrole (CPPy) paper allowed us to significantly improve the catalysis rate, both at the anode and cathode of the fuel cell. The enzymatic cascade on the anode consisted of invertase, mutarotase, Flavine Adenine Dinucleotide (FAD)-dependent glucose dehydrogenase and fructose dehydrogenase. The multi-substrate anode utilized glucose, fructose, sucrose, or a combination of them, as the anode fuel and molecular oxygen were the oxidant at the laccase-based cathode. Laccase was adsorbed on the same type of naphthoquinone modified gold nanoparticles. Interestingly, the naphthoquinone modified gold nanoparticles acted as the enzyme orienting units and not as mediators since the catalyzed oxygen reduction occurred at the potential where direct electron transfer takes place. Thanks to the good catalytic and capacitive properties of the modified electrodes, the power density of the sucrose/oxygen enzymatic fuel cells (EFC) reached 0.81 mW cm−2, which is beneficial for a cell composed of a single cathode and anode.

Design, synthesis and anticancer activity of naphthoquinone derivatives

Basis on molecular docking and pharmacophore analysis of naphthoquinone moiety, a total of 23 compounds were designed and synthesised. With the help of reverse targets searching, anti-cancer activity was preliminarily evaluated, most of them are effective against some tumour cells, especially compound 12: 1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl-4-oxo-4-((4-phenoxyphenyl)amino) butanoate whose IC50 against SGC-7901 was 4.1 ± 2.6 μM. Meanwhile the anticancer mechanism of compound 12 had been investigated by AnnexinV/PI staining, immunofluorescence, Western blot assay and molecular docking. The results indicated that this compound might induce cell apoptosis and cell autophagy through regulating the PI3K signal pathway.

Effect of β-cyclodextrin encapsulation on cytotoxic activity of acetylshikonin against HCT-116 and MDA-MB-231 cancer cell lines

Acetylshikonin (AcSh), as a red colored pigment found in roots of the plants from family Boraginaceae, showed excellent cytotoxic activity. Due to its hydrophobic nature, and thus poor bioavailability, the aim of this study was to prepare acetylshikonin/β-cyclodextrin (AcSh/β-CD) inclusion complex by using coprecipitation method, characterize obtained system by using UV/VIS, IR and 1H NMR spectroscopy, and determine cytotoxic activity. Phase solubility test indicated formation of AL-type binary system (substrate/ligand ratio was 1:1 M/M), with stability constant Ks of 306.01 M−1. Formation of noncovalent bonds between inner layer of the hole of β-CD and AcSh was observed using spectroscopic methods. Notable changes in chemical shifts of two protons (−0.020 ppm) from naphthoquinone moiety (C6-H and C7-H), as well as protons from hydroxyl groups (−0.013 and −0.009, respectively) attached to C5 and C8 carbons from naphthoquinone part indicate that the molecule of AcSh enters the β-CD cavity from the aromatic side. Cytotoxic activity against HCT-116 and MDA-MB-231 cell lines was measured by MTT test and clonogenic assay. Mechanisms of action of free AcSh and inclusion complex were assessed by flow cytometry. In comparison to free AcSh, AcSh/β-CD showed stronger short-term effect on HCT-116 cells and superior long-term effect on both cell lines. Inclusion complex induced more pronounced cell cycle arrest and autophagy inhibition, and induced increase in accumulation of intracellular ROS more effectively than free AcSh. In conclusion, AcSh/β-CD binary system showed better performances regarding cytotoxic activity against tested tumor cell lines.

Electrochemical study of dibenzo-xanthene and dihydrobenzochromono pyrazole derivatives

The electrochemical reduction of 9 substituted aryl-5H-dibenzo[b,i]xanthene-5,7,12,14(13H)-tetraones (DBXT) and 10 substituted 3-methyl-1,4-diphenyl-1,4-dihydrobenzo [6,7]chromeno[2,3-c]pyrazole-5,10 diones (DCPD) in water/DMF mixture (30/70 v/v) has been studied by cyclic voltammetry, choronoamperometry and differential pulse voltammetry at a glassy carbon electrode. Our data show that the electrochemical reduction of DBXTs takes place in two consecutive two-electron processes, ErEq, corresponding to two successive reductions of naphthoquinone moieties to 1,4-naphthalenediol groups (13-phenyl-13H-dibenzo[b,i]xanthene-5,7,12,14-tetraol). On the other hand, electrochemical reduction of DCPDs shows a reversible two-electron process corresponding to the reduction of naphthoquinone moiety to 1,4-naphthalenediol group. Our data also show that DBXT derivatives containing electron-withdrawing groups participate in the comproportionation reaction, while the fully reduced DBXT derivatives with electron-donating groups are unstable and readily undergoes side reactions. The calculated diffusion coefficient of some DBXT (5 × 10−7 cm2/s) and DCPD (2 × 10−7 cm2/s) derivatives shows that there is no significant relationship between the diffusion coefficients and substituent groups. The smaller diffusion coefficient of DCPD than that of the DBXT derivatives can be related to the formation of more and stronger hydrogen bonds by DCPD than DBXT derivatives. In this work, also, the correlation of E1/2 with σ constants and the adsorption behavior of DBXTs and DCPDs has been investigated.

Naphthoquinone-derived polyol macrolides from natural sources

New biologically active substances isolated from natural sources provide valuable information on structural motifs that are important for a specific type of activity and can also be used as drugs or serve as raw materials for chemical modification in order to develop new pharmaceuticals. This review considers natural antibiotics combining two pharmacophores in their structure: a redox-active naphthoquinone moiety and a membrane-active polyol macrolide. Data on their structures and the spectrum of biological activity are summarized.

Chemoselective one-pot access to benzo[e]indole-4,5-diones and naphtho[2,1-b]thiophene-4,5-diones via copper-catalyzed oxidative [3 + 2] annulation of α-oxoketene N,S-acetals/β-ketothioamides with α-/β-naphthols

An operationally simple and efficient one-pot method for the synthesis of 1-aroyl (or alkanoyl)-2-thioalkyl-3-aryl (or alkyl)-3H-benzo[e]indole-4,5-diones and naphtho[2,1-b]thiophene-4,5-diones has been devised by copper-catalyzed cross-coupling of α-oxoketene N,S-acetals/β-ketothioamides with α-/β-naphthols in open air for the first time. The key to the success of this transformation is the room temperature oxidation of α-/β-naphthol to 1,2-naphthoquinone as a reactive species, which undergoes formal [3 + 2] annulation with α-oxoketene N,S-acetals/β-ketothioamides via cascade sequence of Michael addition/tautomerization/oxidation/cyclization/aromatization reactions, enabling addition of a pyrrole/thiophene ring onto naphthoquinone moiety. Further, benzo[e]indole-4,5-diones were transformed to pentacyclic fused phenazine derivatives under solvent-free conditions. Based on our experimental outcomes, a tentative mechanistic rationale for this chemoselective protocol is proposed, which is well validated and supported by the control experiments.

Theoretical investigation of the photophysical properties of donor-acceptor dyes containing coumarin and naphthoquinone moieties linked by an aminomethylene bridge

Mannich bases HL1 and HL2 derived from lawsone, heptylamine and 3-formylcoumarins have been synthesized for the investigation of their photophysical properties. The cyclic voltammetry data showed a charge transfer (CT) process from the coumaryl to the naphthoquinonoid group, in spite of the absence of conjugation between these two fragments, with the nitrogen atom playing an important role. Photophysical studies by UV–Visible and fluorescence spectroscopy in acetonitrile revealed low emission quantum yield (Φ), thus confirming the quenching of the coumarin fluorophore by the naphthoquinone moiety. The role of the nitrogen atom in this spacer was investigated by perturbing the electronic density at this site by protonation. The emission spectra of the hydrochlorides HL1·HCl and HL2·HCl revealed increase in the quantum yields in both cases. The geometries of all compounds were optimized at B3LYP/6-31 + G (d,p) level. TD-DFT calculations were carried out with different functionals. The hybrids B3LYP and PBE0 provided the best results with respect to the lowest energy transition and M06-HF failed in this prediction, whereas the long range corrected functionals - CAM-B3LYP and ωB97XD - did not improve the description of this transition. For HL1 and HL2, the lowest energy absorption band around 440 nm (λ3) is assigned to an aminomethyl coumarin (HOMO-1) to naphthoquinone (LUMO) CT. However, for HL1·HCl and HL2·HCl, the contribution of the nitrogen atom was suppressed by protonation and the lowest energy transition is assigned only to the coumarin (HOMO) to naphthoquinone (LUMO) CT.

New Naphthoquinone Terpenoids from Marine Actinobacterium, Streptomyces sp. CNQ-509.

A member of the marine streptomycete clade MAR4, Streptomyces sp. CNQ-509, has genetic potential for the biosynthesis of hybrid isoprenoids and produces several meroterpenoids such as naphterpin, nitropyrrolin and marinophenazine. Our research on the strain CNQ-509 led to the isolation of two new naphterpin derivatives (1 and 2) comprised of naphthoquinone and geranyl moieties along with the known terpenoid, debromomarinone. The two-dimensional structure of these compounds was determined through spectral data analysis using data from NMR, MS and UV spectroscopy. Furthermore, the full structures of 1 and 2 including absolute configurations were unequivocally established by a combination of NMR experiments and chemical modifications.