Design, Synthesis, and Fungicidal Activities of Novel N-(Pyrazol-5-yl)benzamide Derivatives Containing a Diphenylamine Moiety.

To accelerate the development of novel fungicides, a variety of N-(pyrazol-5-yl)benzamide derivatives with a diphenylamine moiety were designed and synthesized using a pharmacophore recombination strategy based on the structure of pyrazol-5-yl-aminophenyl-benzamides. The bioassay results demonstrated that most of the target compounds had excellent in vitro antifungal activities against Sclerotinia sclerotiorum, Valsa mali, and Botrytis cinerea. In particular, compound 5IIIh exhibited remarkable activity against S. sclerotiorum (EC50 = 0.37 mg/L), which was similar to that of fluxapyroxad (EC50 = 0.27 mg/L). In addition, compound 5IIIc (EC50 = 1.32 mg/L) was observed to be more effective against V. mali than fluxapyroxad (EC50 = 12.8 mg/L) and comparable to trifloxystrobin (EC50 = 1.62 mg/L). Furthermore, compound 5IIIh demonstrated remarkable in vivo protective antifungal properties against S. sclerotiorum, with an inhibition rate of 96.8% at 100 mg/L, which was close to that of fluxapyroxad (99.6%). Compounds 5IIIc (66.7%) and 5IIIh (62.9%) exhibited good in vivo antifungal effects against V. mali at 100 mg/L, which were superior to that of fluxapyroxad (11.1%) but lower than that of trifloxystrobin (88.9%). The succinate dehydrogenase (SDH) enzymatic inhibition assay was conducted to confirm the mechanism of action. Molecular docking analysis further revealed that compound 5IIIh has significant hydrogen-bonding, π-π, and p-π conjugation interactions with ARG 43, SER 39, TRP 173, and TYR 58 in the binding site of SDH, and the binding mode was similar to that of the commercial fungicide fluxapyroxad. All of the results suggest that compound 5IIIh could be a potential SDH inhibitor, offering a valuable reference for future studies.

Integration of iron-manganese layered double hydroxide/tungsten carbide composite: An electrochemical tool for diphenylamine H•+ analysis in environmental samples.

Incompetent governance of post-harvest horticultural crops especially apples and pears lead to numerous physiological storage disorders. In order to manage this issue, diphenylamine (DPA) is widely used as an antioxidant and anti-scald agent to preserve fruits from superficial scalds and degradation during storage. As a result, this research focuses on utilizing disposable electrodes constructed with sphere-shaped iron-manganese layered double hydroxide (FeMn-LDH) entrapped tungsten carbide (WC) nanocomposite on its electrochemical performances towards emergent food contaminant, DPA. The importance of the current work is the selection and design of hierarchically structured functional materials especially layered double hydroxides, in virtue of their outstanding properties. These multi-dimensional structures when introduced to form a composite with the highly beneficial tungsten carbide offer excellent characteristics such as exceptional accessibility to active sites, enhanced surface area, and high mass transport and diffusion which serves as advantageous for the electrochemical quantification of DPA. Furthermore, the synergy between FeMn-LDH and WC nanomaterials contributes to the higher active surface area, increased electrical conductivity, fast electron transportation, and ion diffusion, resulting in static properties including a wide linear range (0.01-183.34 µM), low detection limit (1.1 nM), greater sensitivity, selectivity, and reproducibility thus confirming the potential capability of the WC@FeMn-LDH sensor towards the interference-free determination of DPA which validates its practicality and feasibility in real-time. Hence, this work aims to stimulate the fabrication of various advanced hierarchical structures by a simple hydrothermal approach that can have veracity of potential applications.

Impacts of diphenylamine NSAID halogenation on bioactivation risks.

Diphenylamine NSAIDs are highly prescribed therapeutics for chronic pain despite causing symptomatic hepatotoxicity through mitochondrial damage in five percent of patients taking them. Differences in toxicity are attributed to structural modifications to the diphenylamine scaffold rather than its inherent toxicity. We hypothesize that marketed diphenylamine NSAID substituents affect preference and efficiency of bioactivation pathways and clearance. We parsed the FDA DILIrank hepatotoxicity database and modeled marketed drug bioactivation into quinone-species metabolites to identify a family of seven clinically relevant diphenylamine NSAIDs. These drugs fell into two subgroups, i.e., acetic acid and propionic acid diphenylamines, varying in hepatotoxicity risks and modeled bioactivation propensities. We carried out steady-state kinetic studies to assess bioactivation pathways by trapping quinone-species metabolites with dansyl glutathione. Analysis of the glutathione adducts by mass spectrometry characterized structures while dansyl fluorescence provided quantitative yields for their formation. Resulting kinetics identified four possible bioactivation pathways among the drugs, but reaction preference and efficiency depended upon structural modifications to the diphenylamine scaffold. Strikingly, diphenylamine dihalogenation promotes formation of quinone metabolites through four distinct metabolic pathways with high efficiency, whereas those without aromatic halogen atoms were metabolized less efficiently through two or fewer metabolic pathways. Overall metabolism of the drugs was comparable with bioactivation accounting for 4-13% of clearance. Lastly, we calculated daily bioload exposure of quinone-species metabolites based on bioactivation efficiency, bioavailability, and maximal daily dose. The results revealed stratification into the two subgroups; propionic acid diphenylamines had an average four-fold greater daily bioload compared to acetic acid diphenylamines. However, the lack of sufficient study on the hepatotoxicity for all drugs prevents further correlative analyses. These findings provide critical insights on the impact of diphenylamine bioactivation as a precursor to hepatotoxicity and thus, provide a foundation for better risk assessment in drug discovery and development.

Multicomponent synthesis and preliminary anti-inflammatory activity of lipophilic diphenylamines.

Non-Steroidal Anti-inflammatory Drugs (NSAIDs) are some of the most prescribed medications for pain but the incidence of adverse effects -especially during chronic treatment- points out the requirement of new analgesics. In this study, we showed an efficient two-steps synthesis of diphenylamine-containing dipeptides consisting of a multicomponent process followed by a Buchwald-Hartwig cross-coupling reaction. We prepared 16 diphenylamine derivatives and evaluated their in vivo anti-inflammatory activity through an ear edema model using 12-O-tetradecanoylpholbol-13-acetate. Furthermore, the toxicity of the more potent compounds in the Artemia salina model and their cell viability using murine RAW 264.7 cells is reported. The fluorinated compound 10k becomes a reliable candidate since it reduced the TPA-induced edema to 92%, lacked cytotoxicity against murine macrophages, and had minimal toxicity in Artemia salina.

Synthesis and characterization of diphenylamine grafted onto sodium alginate for metal removal.

A novel grafting polymer was synthesized via grafting of diphenylamine (DPA) onto sodium alginate (NaAlg) as a new adsorbent for Cobalt (Co2+) from aqueous solutions. Optimization of sodium alginate grafted by diphenylamine (NaAlg-g-DPA) was addressed in the current study by several parameters including; initiator and monomer concentrations, contact time of polymerization, as well as polymerization temperature. In addition, the structural and chemical characteristics of NaAlg-g-DPA were explored using different modalities later. The results showed that sodium alginate grafted by diphenylamine (NaAlg-g-DPA) is suitable for adsorbent to removal Co2+ ion. The parameters for the adsorption of Co(II) ions by NaAlg-g-DPA were also determined. It was shown that the samples of NaAlg-g-DPA had given good correlation with Temkins isotherm model and their kinetics followed pseudo-second-order model. It was also observed that the adsorption capacity seemed to be dependent on pH value in solution which showed better results at basic pH. The findings from this research show that NaAlg-g-DPA has capability to remove Co (II) from aqueous solutions.

Small molecule inhibitors and culture conditions enhance therapeutic cell and EV potency via activation of beta-catenin and suppression of THY1.

Primary cell therapy continues to face significant hurdles to therapeutic translation including the inherent variations that exist from donor to donor, batch to batch, and scale-up driven modifications to the manufacturing process. Cardiosphere-derived cells (CDCs) are stromal/progenitor cells with clinically demonstrated tissue reparative capabilities. Mechanistic investigations have identified canonical Wnt/ß-catenin signaling as a therapeutic potency marker, and THY1 (CD90) expression as inversely correlated with potency. Here we demonstrate that the cardiosphere formation process increases ß-catenin levels and enriches for therapeutic miR content in the extracellular vesicles of these cells, namely miR-146a and miR-22. We further find that loss of potency is correlated with impaired cardiosphere formation. Finally, our data show that small GSK3ß inhibitors including CHIR, and BIO and "pro-canonical Wnt" culturing conditions can rescue ß-catenin signaling and reduce CD90 expression. These findings identify strategies that could be used to maintain CDC potency and therapeutic consistency.

Metabolically stable diphenylamine derivatives suppress androgen receptor and BET protein in prostate cancer.

Androgen receptor (AR) is a crucial driver of prostate cancer (PC). AR-relevant resistance remains a major challenge in castration-resistant prostate cancer (CRPC). Bromodomain and extra-terminal domain (BET) family are critical AR coregulators. Here, we developed several diphenylamine derivatives and identified compound 7d that disrupted the functions of AR and BET family in prostate cancer and exhibited favorable metabolic stability in vitro and high drug exposure in vivo. We showed 7d not only bound to AR, suppressed transactivation of wild-type AR (wt-AR) and the mutant that mediates Enzalutamide resistance, but also reduced c-Myc protein expression through BET inhibition. In addition, 7d inhibited the proliferation of AR-positive PC cells with favorable selectivity and suppressed AR-V7-expressing VCaP and 22Rv1 xenografts growth in vivo. Collectively, these results indicate the potential of lead compound 7d as an orally available AR and BET inhibitor to treat CRPC and overcome antiandrogen resistance.

Targeting phosphatidylethanolamine and phosphatidylserine for imaging apoptosis in cancer.

INTRODUCTION: Both phosphatidylethanolamine (PE) and phosphatidylserine (PS) can be externalized to the outer cell membrane in apoptosis. Thus the objective was to determine whether PE-targeting 18F-duramycin and PS-targeting 18F-Zn-DPA could be used for imaging apoptosis. METHODS: Duramycin and Zn-DPA were labeled with either 18F-Al or 18F-SFB. U937 cells were incubated with four different concentrations of camptothecin (CPT). For assessing the effect of incubation time on uptake, 37 MBq of radiotracer was added to cells incubated for 15, 30, 60, and 120 min at 37 °C. For blocking experiments, 150 µg duramycin and 40 µg Zn-DPA were added to cells for 15 min prior to the addition of either duramycin or Zn-DPA labeled with 18F. Apoptosis was measured by flow cytometry using an annexin-V/PI kit. Cells were co-stained with Hoechst, Cy5-duramycin, and PSVue480 (FITC-Zn-DPA) to localize fluorescent dye uptake in cells. RESULTS: Apoptosis in cells increased proportionally with CTP as confirmed by both flow cytometry and fluorescent staining. Both FITC-Zn-DPA and FITC-duramycin localized mainly on the cell membrane during early apoptosis and then translocated to the inside during late apoptosis. Uptake of FITC-duramycin, however, was higher than that of FITC-Zn-DPA. Cellular uptake of four different radiotracers was also proportional to the degree of apoptosis, increasing slightly over time and reaching a plateau at about 1 h. The blocking experiments demonstrated that uptake in all the control groups was predominantly non-specific, whereas the specific uptake in all the treated groups was at least 50% for both 18F labeled duramycin and Zn-DPA. CONCLUSION: Both PE-targeting 18F-duramycin and PS-targeting 18F-Zn-DPA could be considered as potential radiotracers for imaging cellular apoptosis. Advances in knowledge and implications for patient care: Cellular data support the further development of radiotracers targeting either PE or PS for imaging apoptosis, which can associate with clinical outcome for cancer patients.

Design, Synthesis, and Antifungal Activities of Novel Aromatic Carboxamides Containing a Diphenylamine Scaffold.

A series of novel N-(2-(phenylamino)-4-fluorophenyl)-pyrazole-4-carboxamides 1-15 and aromatic carboxamides with a diphenylamine scaffold 16-29 were designed, synthesized, and evaluated for their antifungal activities. In vitro experiments showed that compound 6 (EC50 = 0.03 mg/L) was superior to bixafen (EC50 = 0.04 mg/L) against Rhizoctoinia solani and compound 6 (IC50 = 1.41 mg/L) was close to bixafen (IC50 = 1.22 mg/L) against succinate dehydrogenase from R. solani. Additionally, in vivo pot experiments showed that compound 6 (EC50 = 1.93 mg/L) was better than bixafen (EC50 = 3.72 mg/L) and close to thifluzamide (EC50 = 1.83 mg/L) against R. solani. In vivo field trials showed that compound 6 at 200 g ai ha-1 had 64.10% control efficacy against rice sheath blight after 21 days with two sprayings, close to thifluzamide (71.40%). Furthermore, molecular docking showed that compound 6 anchors in the binding site of SDH.

Synthesis of Meso-Diarylaminocorroles via SNAr Reactions.

A corrole is a tetrapyrrolic macrocycle known as a ring-contracted porphyrinoid. Despite the progress of the synthetic chemistry of meso-aryl-substituted corroles since the early 2000s, meso-heteroatom-substituted corroles have been scarcely reported. Herein we report that the SNAr-type substitution reaction of a meso-chlorocorrole silver complex with diphenylamine or carbazole in the presence of NaH as a base produced meso-aminocorroles. The structures, ultraviolet⁻visible spectroscopy (UV/Vis), and emission spectra of these meso-aminocorroles were discussed. Furthermore, the oxidation reaction of a meso-diphenylaminocorrole was examined, which resulted in the formation of 10,10-diethoxyisocorrole.

Electrochemical detection of toxic anti-scald agent diphenylamine using oxidized carbon nanofiber encapsulated titanium carbide electrocatalyst.

Two dimensional (2D) titanium carbide (Ti-C) is an analogues of graphene have tremendous attention in recent years due to their high electrical conductivity and catalytic activity. Herein, we have synthesized Ti-C micro particles based on the template-assisted method and subsequently integrated with oxidized carbon nanofiber (f-CNF) through ultrasonication technique. The prepared Ti-C/f-CNF composite was subjected to various structural and morphological characterization techniques including the X-ray diffraction (XRD), scanning electron microscope (SEM), Energy Dispersive X-ray (EDX) and X-ray photoelectron spectroscopy (XPS). The all followed studies confirmed the formation and crystalline nature of prepared Ti-C/f-CNF nanocomposite. Further, the proposed Ti-C/f-CNF composite modified electrode was successfully applied as an electrocatalyst for the electrochemical detection of diphenylamine (DPA) in food. DPA is known as an anti-scald agent used to post harvest treatment of fruits. However, the higher concentration of DPA causes some hazardous side effects to human. Thus, the detection of DPA is an important concern in healthcare research. Eventually, the proposed Ti-C/f-CNF/SPCE exhibited ultra-low detection limit of (0.003 µM) with a linear range of 0.04-56.82 µM towards the detection of DPA. Moreover, the practicability of the proposed sensor was tested by real sample analysis by using fresh apple extract. Remarkably, the proposed sensor showed an excellent recovery range from 106.8% to 108% for the detection of DPA in spiked apple extract. Finally, we concluded that the integration of f-CNF with Ti-C is significantly enhanced both electrical conductivity and electrocatalytic activity for sensor application.

Synthesis of diphenylamine macrocycles and their anti-inflammatory effects.

A collection of fourteen diphenylamine macrocyclic derivatives containing a peptide chain with different substituents was synthesized using a protocol of two Ugi four component reactions (Ugi-4CR) and a Buchwald-Hartwig macrocyclization. Their anti-inflammatory effects were assayed with an ear edema model using 12-O-tetradecanoylphorbol-13-acetate, while the activity of myeloperoxidase was determined to evaluate the index of leukocyte infiltration. Compound 5e had an ID50 of 0.18 µM per ear with a potency higher than that of the reference drugs indomethacin and celecoxib (0.24 and 0.91 µM per ear, respectively). Moreover, the cytotoxicity of the macrocycles was determined in two healthy cell lines, showing a low percentage of toxicity.

Relative molar sensitivities of carnosol and carnosic acid with respect to diphenylamine allow accurate quantification of antioxidants in rosemary extract.

We have been developing a high-performance liquid chromatography/photodiode array (HPLC/PDA) employing relative molar sensitivities (RMSs) and adopted it to the accurate quantification of carnosol (CL) and carnosic acid (CA) which are the antioxidants in rosemary extract. The method requires no references of CL or CA and instead uses RMSs with respect to diphenylamine (DPA) whose certified reference material is available from a reagent manufacturer. The molar and response ratios of the analytes to the reference in an artificial mixture of them were determined using 1H-quantitative nuclear magnetic resonance spectroscopy (1H-qNMR) and HPLC/PDA at a wavelength of 284 nm under isocratic condition, respectively, and then RMSs were calculated to be 0.111 for CL/DPA and 0.0809 for CA/DPA as averaged values in three HPLC-PDA instruments. The RMS values varied by up to 1.1% as relative standard deviation. To evaluate the performance of HPLC/PDA with the RMSs, the CL and CA contents in rosemary extracts were determined using DPA as a reference. The CL and CA contents were compared with those determined using calibration curves of CL and CA obtained by HPLC measurement of standard solutions prepared from their reagents whose absolute purities were determined using 1H-qNMR. The differences between the two methods for CL and CA were ≤3% as relative error. This chromatographic method with RMSs allows a simple and reliable quantification when reference of the analyte is unavailable.

A turn-on fluorescence probe based on aggregation-induced emission for leucine aminopeptidase in living cells and tumor tissue.

Abnormally-expressed leucine aminopeptidase (LAP) is associated with diverse physiological and pathological disorders; hence developing a highly selective and sensitive detection system for LAP is of great significance. Herein, a fluorescent light-up system with aggregation-induced emission (AIE) characteristic, (DPA-TPE-Leu) has been developed for detecting LAP, in which the recognition unit l-leucine amide group also acts as the hydrophilic moiety. Upon LAP-triggered enzymatic reaction, l-leucine amide moiety is cleaved from the probe molecule, resulting in the formation and aggregation of the hydrophobic reaction product (DPE-TPE-OH) with AIE effect and thus giving out the turn-on green fluorescence. The system features excellent photostability, large Stokes shift (194 nm), good water solubility, high sensitivity with the detection limit of 0.16 U L-1, favorable specificity and low cytotoxicity. It has been effectively utilized in fluorescent imaging of endogenous LAP in living cells, and also successfully applied for fluorescent imaging of HepG2 xenograft tumor. Such a fluorescent assay could provide a convenient and sensitive method for detecting LAP activity and might aid in the auxiliary diagnosis of hepatocellular carcinoma and related pathological analysis in biopsy.

An Optical Dosimeter for the Selective Detection of Gaseous Phosgene with Ultralow Detection Limit.

We present here a cheap, fast, and highly selective dosimeter for the colorimetric detection of gaseous phosgene with an ultralow detection limit. The disposable device is based on Harrison's reagent supported into a porous nanocrystalline TiO2 matrix film. We exposed the films to phosgene streams while the absorbance was monitored by an optic fiber in a gas chamber. The pronounced spectral changes were unaffected by humidity and oxygen and permitted us to use the response rate at 464 nm as a very stable calibration signal for quantitative analysis purposes. The use of a specific sensing reaction guaranteed a very high selectivity of the device even against saturated vapors of primary interferences like halide gases and other oxidizing and volatile agents. With this simple method, whose response is compatible with affordable and efficient miniature LED-photodiode devices, we reach an ultralow limit of detection well below the ppm level.

A biomaterial screening approach reveals microenvironmental mechanisms of drug resistance.

Traditional drug screening methods lack features of the tumor microenvironment that contribute to resistance. Most studies examine cell response in a single biomaterial platform in depth, leaving a gap in understanding how extracellular signals such as stiffness, dimensionality, and cell-cell contacts act independently or are integrated within a cell to affect either drug sensitivity or resistance. This is critically important, as adaptive resistance is mediated, at least in part, by the extracellular matrix (ECM) of the tumor microenvironment. We developed an approach to screen drug responses in cells cultured on 2D and in 3D biomaterial environments to explore how key features of ECM mediate drug response. This approach uncovered that cells on 2D hydrogels and spheroids encapsulated in 3D hydrogels were less responsive to receptor tyrosine kinase (RTK)-targeting drugs sorafenib and lapatinib, but not cytotoxic drugs, compared to single cells in hydrogels and cells on plastic. We found that transcriptomic differences between these in vitro models and tumor xenografts did not reveal mechanisms of ECM-mediated resistance to sorafenib. However, a systems biology analysis of phospho-kinome data uncovered that variation in MEK phosphorylation was associated with RTK-targeted drug resistance. Using sorafenib as a model drug, we found that co-administration with a MEK inhibitor decreased ECM-mediated resistance in vitro and reduced in vivo tumor burden compared to sorafenib alone. In sum, we provide a novel strategy for identifying and overcoming ECM-mediated resistance mechanisms by performing drug screening, phospho-kinome analysis, and systems biology across multiple biomaterial environments.

Pharmacological use of a novel scaffold, anomeric N,N-diarylamino tetrahydropyran: molecular similarity search, chemocentric target profiling, and experimental evidence.

Rational drug design against a determined target (disease, pathway, or protein) is the main strategy in drug discovery. However, regardless of the main strategy, chemists really wonder how to maximize the utility of their new compounds by drug repositioning them as clinical drug candidates in drug discovery. In this study, we started our drug discovery "from curiosity in the chemical structure of a drug scaffold itself" rather than "for a specific target". As a new drug scaffold, anomeric diarylamino cyclic aminal scaffold 1, was designed by combining two known drug scaffolds (diphenylamine and the most popular cyclic ether, tetrahydropyran/tetrahydrofuran) and synthesized through conventional Brønsted acid catalysis and metal-free α-C(sp3)-H functionalized oxidative cyclization. To identify the utility of the new scaffold 1, it was investigated through 2D and 3D similarity screening and chemocentric target prediction. The predicted proteins were investigated by an experimental assay. The scaffold 1 was reported to have an antineuroinflammatory agent to reduce NO production, and compound 10 concentration-dependently regulated the expression level of IL-6, PGE-2, TNF-α, ER-ß, VDR, CTSD, and iNOS, thus exhibiting neuroprotective activity.

Occurrence and fate of substituted diphenylamine antioxidants and benzotriazole UV stabilizers in various Canadian wastewater treatment processes.

Substituted diphenylamine antioxidants (SDPAs) and benzotriazole UV stabilizers (BZT-UVs) are additives used in industrial and consumer products to prevent degradation or color change of materials, but their environmental fate and disposition are not well characterized. In this study, SDPAs and BZT-UVs were analyzed in 68 liquid and 39 solid samples collected from 9 wastewater treatment plants (WWTPs) in Canada to investigate the occurrence and fate of these contaminants. The median concentrations of ΣSDPAs and ΣBZT-UVs was 483 and 76.2 ng L-1 in influent, 28.4 and 4.84 ng L-1 in effluent, and 2750 and 457 ng g-1 in biosolids (dry weight), respectively. Dinonyl-diphenylamine (C9C9) was the predominant congener of SDPAs in all matrices (>40%). For target BZT-UVs, the major components were 2-(2H-benzotriazol-2-yl)-4,6-bis(1-methyl-1-phenylethyl)phenol (UV234) and 2-(2H-benzotriazol-2-yl)-4,6-di-tert-pentylphenol (UV328). SDPAs and BZT-UVs were effectively removed (>90%) from the liquid stream in most WWTPs mainly through sludge sorption and separation, but biotransformation, UV treatment and filtration may also contribute to removal of some contaminants in advanced treatment plants. In contrast, the removal efficiency of target contaminants using chemically assisted primary treatment was low, likely due to the short hydraulic retention time of this site. Our results suggest that wastewater effluent is a vector of SDPAs and BZT-UVs to the aquatic environment. The results also highlight the high concentrations of SDPAs and BZT-UVs associated with the solid stream in WWTPs, which could affect the beneficial use of biosolids (e.g., compost or land applications).

Incorporation of spheroidene and spheroidenone into light-harvesting complexes from purple sulfur bacteria.

Spheroidene and spheroidenone from the non-sulfur bacterium Rhodobacter (Rba.) sphaeroides were incorporated into diphenylamine (DPA) LH1-RC and LH2 complexes from sulfur bacteria Allochromatium (Alc.) minutissimum and Ectothiorhodospira (Ect.) haloalkaliphila in which carotenoid (Car) biosynthesis was inhibited by ~95%. A series of biochemical characteristics of the modified LH2 complexes was studied (electrophoretic mobility, absorption and CD spectra, Car composition, Car-to-BChl energy transfer and thermal stability). It was found that the electrophoretic mobility of the complexes with incorporated Cars did not change compared to that of the control and DPA-complexes, indicating the absence of any significant change in the structure of LH complexes upon DPA-treatment and subsequent incorporation of Cars. The analysis of fluorescence excitation spectra of the spheroidene-incorporated LH2 complex (LH2:sph) and the spheroidenone-incorporated LH2 complex (LH2:sph-ne) showed that spheroidene and spheroidenone exhibited relatively low efficiencies of energy transfer to BChl, when incorporated into the LH2 DPA-complexes from Alc. minutissimum and Ect. haloalkaliphila, although, they showed high efficiencies, being in their natural state in the LH2 complexes from Rba. sphaeroides. A significant increase in thermostability observed for the LH2:sph and LH2:sph-ne complexes with respect to the LH2 DPA-complexes indicated that the two incorporated Cars stabilized the structure of the LH2 complexes.

Design, synthesis and antifungal activity of novel fenfuram-diarylamine hybrids.

Ten novel fenfuram-diarylamine hybrids were designed and synthesized. And their antifungal activities against four phytopathogenic fungi have been evaluated in vitro and most of the compounds demonstrated a significant antifungal activities against Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 5e exhibited the most potent antifungal activity against R. solani with an EC50 value of 0.037mg/L, far superior to the commercially available fungicide boscalid (EC50=1.71mg/L) and lead fungicide fenfuram (EC50=6.18mg/L). Furthermore, scanning electron microscopy images showed that the mycelia on treated media grew abnormally with tenuous, wizened and overlapping colonies compared to the negative control. Molecular docking studies revealed that compound 5e featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 3-chlorophenyl group in compound 5e formed a CH-π interaction with B/Trp-206 and a Cl-π interaction with D/Tyr-128, rendering compound 5e more active than fenfuram against SDH.