Methoxy Analogue Research Articles

Pyrrolidine derivatives as α-amylase and α-glucosidase inhibitors: Design, synthesis, structure-activity relationship (SAR), docking studies and HSA binding

In our pursuit of developing effective inhibitors for the enzymes α-amylase and α-glucosidase, which play a crucial role in carbohydrate metabolism related to type-2 diabetes, we synthesized compounds featuring a pyrrolidine ring. The synthesis involved coupling N-Boc-proline with various aromatic amines, resulting in the formation of distinct N-Boc proline amides. To investigate the influence of the Boc group on enzyme inhibition, the Boc group was subsequently removed. In vitro, testing against α-amylase and α-glucosidase, with metformin and acarbose as reference standards, revealed that the 4-methoxy analogue 3g showed noteworthy inhibitory activity, with IC50 values of 26.24 and 18.04 μg/mL, respectively. Compounds 3a with an IC50 value of 36.32 μg/mL and 3f with an IC50 value of 27.51 μg/mL displayed significant inhibitory activity against α-amylase and α-glucosidase, respectively. The results of molecular docking studies of the most potent pyrrolidine derivatives 3a and 3g with α-amylase and 3f and 3g with α-glucosidase showed good agreement with experimental data. Moreover, compound 3g showed strong binding interactions with HSA having binding constant values of 7.08 × 105 M−1 and 4.77 × 105 M−1 using UV–visible and fluorescence spectrophotometry, respectively.

Alkoxy chain length governs the potency of 2-benzylbenzimidazole 'nitazene' opioids associated with human overdose.

Novel synthetic opioids (NSOs) are emerging in recreational drug markets worldwide. In particular, 2-benzylbenzimidazole 'nitazene' compounds are problematic NSOs associated with serious clinical consequences, including fatal respiratory depression. Evidence from in vitro studies shows that alkoxy chain length can influence the potency of nitazenes at the mu-opioid receptor (MOR). However, structure-activity relationships (SARs) of nitazenes for inducing opioid-like effects in animal models are not well understood compared to relevant opioids contributing to the ongoing opioid crisis (e.g., fentanyl). Here, we examined the in vitro and in vivo effects of nitazene analogues with varying alkoxy chain lengths (i.e., metonitazene, etonitazene, isotonitazene, protonitazene, and butonitazene) as compared to reference opioids (i.e., morphine and fentanyl). Nitazene analogues displayed nanomolar affinities for MOR in rat brain membranes and picomolar potencies to activate MOR in transfected cells. All compounds induced opioid-like effects on locomotor activity, hot plate latency, and body temperature in malemice, and alkoxy chain length markedly influenced potency. Etonitazene, with an ethoxy chain, was the most potent analogue in MOR functional assays (EC50 = 30pM, Emax = 103%) and across all in vivo endpoints (ED50 = 3-12μg/kg). In vivo SARs revealed that ethoxy, isopropoxy, and propoxy chains engendered higher potencies than fentanyl, whereas methoxy and butoxy analogues were less potent. MOR functional potencies, but not MOR affinities, were positively correlated with in vivo potencies to induce opioid effects. Overall, our data show that certain nitazene NSOs are more potent than fentanyl as MOR agonists in mice, highlighting concerns regarding the high potential for overdose in humans who are exposed to these compounds.

Synthesis and X-ray diffraction analysis of coenzyme Q derivatives obtained from natural polyalkoxyallylbenzenes

A general synthetic access to methoxy analogues of coenzymes Q bearing functional substituents with various chain lengths at the quinone ring was developed using available natural (polymethoxy)(methylenedioxy)allylbenzenes. The Baeyer–Villiger rearrangement of (methylenedioxy)benzaldehydes into phenols followed by facile oxidation to quinones with the methylenedioxy moiety opening was identified as the key step in the synthesis of the target 1,4- and 1,2-polyalkoxyquinones

Separation and Identification of Related Substances in Candesartan Cilexetil Tablets by UHPLC-Q-TOF–MS

Related substances, such as process-related substances and degradation products, may affect the efficacy of drugs and cause adverse reactions. Therefore, identifying and controlling them is of the importance. A rapid ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF–MS) method has been developed for the separation and characterization of related substances in candesartan cilexetil tablets. After optimization, the method validation was followed according to ICH guidelines. The developed UHPLC method showed adequate specificity, sensitivity, accuracy, linearity, precision, stability and robustness for validation of analytical procedures. Commercial candesartan cilexetil tablets was subjected to stress testing (60 ℃, 90% RH and 4500 lx for ten days) and forced degradation studies (acidic, alkaline, oxidative and photolytic degradation conditions). A total of eleven related substances were detected and characterized. Among them, four related substances have not been reported in the literature yet, and one of them (RS7) was confirmed as candesartan cilexetil methoxy analog by reference substance. In addition, plausible mechanisms for the formation of these related substances are discussed. This study provides a useful reference for the quality control of candesartan cilexetil tablets.

The Role of Acetyl Zingerone and Its Derivatives in Inhibiting UV-Induced, Incident, and Delayed Cyclobutane Pyrimidine Dimers.

Cyclobutane pyrimidine dimers (CPDs) are ultraviolet radiation (UV)-induced carcinogenic DNA photoproducts that lead to UV signature mutations in melanoma. Previously, we discovered that, in addition to their incident formation (iCPDs), UV exposure induces melanin chemiexcitation (MeCh), where UV generates peroxynitrite (ONOO-), which oxidizes melanin into melanin-carbonyls (MCs) in their excited triplet state. Chronic MeCh and energy transfer by MCs to DNA generates CPDs for several hours after UV exposure ends (dark CPD, dCPDs). We hypothesized that MeCh and the resulting dCPDs can be inhibited using MeCh inhibitors, and MC and ONOO- scavengers. Here, we investigated the efficacy of Acetyl Zingerone (AZ), a plant-based phenolic alkanone, and its chemical analogs in inhibiting iCPDs and dCPDs in skin fibroblasts, keratinocytes, and isogenic pigmented and albino melanocytes. While AZ and its methoxy analog, 3-(4-Methoxy-benzyl)-Pentane-2,4-dione (MBPD) completely inhibited the dCPDs, MBPD also inhibited ~50% of iCPDs. This suggests the inhibition of ~80% of total CPDs at any time point post UV exposure by MBPD, which is markedly significant. MBPD downregulated melanin synthesis, which is indispensable for dCPD generation, but this did not occur with AZ. Meanwhile, AZ and MBPD both upregulated the expression of nucleotide excision repair (NER) pathways genes including Xpa, Xpc, and Mitf. AZ and its analogs were non-toxic to the skin cells and did not act as photosensitizers. We propose that AZ and MBPD represent "next-generation skin care additives" that are safe and effective for use not only in sunscreens but also in other specialized clinical applications owing to their extremely high efficacy in blocking both iCPDs and dCPDs.

Experimental and theoretical insights into the structure and molecular dynamics of 2,3,3',4'-tetramethoxy-trans-stilbene - a chemopreventive agent.

The methoxy analogue of a trans-stilbene compound - 2,3,3',4'-tetramethoxy-trans-stilbene - was selected to characterize its crystallographic structure, intermolecular interactions and molecular dynamics. The sample was studied using single-crystal X-ray diffraction (XRD), infrared spectroscopy (FT-IR), liquid and solid-state 1H and 13C nuclear magnetic resonance (NMR) and quasielastic neutron scattering (QENS). The compound crystallized in the orthorhombic Pbca space group. The experimental methods were supported by theoretical calculations, density functional theory (plane-wave DFT) and molecular dynamics simulations (MD) methods. Combining several experimental and simulation techniques allowed the detailed analysis of molecular reorientations and provided a consistent picture of the molecular dynamics. The internal molecular mobility of the studied compound can be associated with the reorientational dynamics of four methyl groups. Interestingly, a large diversity of the energy barriers was observed - one methyl group reoriented across low activation barriers (∼3 kJ mol-1), while three methyl groups exhibited a high activation energy (10-14 kJ mol-1) and they are characterised by very different correlation times differing by almost two orders of magnitude at room temperature. The intramolecular interactions mainly influence the activation barriers.

Investigation of Antistress and Antidepressant Activities of Synthetic Curcumin Analogues: Behavioral and Biomarker Approach.

Depression is a serious psychiatric disorder that affects millions of individuals all over the world, thus demanding special attention from researchers in order to investigate its effective remedies. Curcumin, along with its synthetic derivatives, is recognized for its incredible pharmacological activities. In this study, methyl, methoxy and chloro-substituent synthetic curcumin analogues C1–C3 were respectively tested for free radical-scavenging activity. Behavioral studies were performed using chemical-induced and swimming endurance tests as stress models, and forced swim tests (FSTs) and tail suspension tests (TSTs) as depression mice models. Biochemical examinations were performed after a scopolamine-induced stress model by decapitating the mice, and brain tissues were isolated for biochemical assessment of catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA). The curcumin analogue C2 exhibited higher DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azinobis-3-ethylbenzothiazo-line-6-sulphonate) free radical-scavenging potential, having IC50 values of 45.18 µg/mL and 62.31 µg/mL, respectively, in comparison with reference curcumin and tocopherol. In the chemical-induced test, C2 (80.17%), C3 (72.79%) and C1 (51.85%) revealed higher antistress responses by significantly reducing the number of writhes, whereas the immobility time was significantly reduced by C2 and C3 in the swimming endurance test, indicating excellent antistress potential. Similarly, C2 and C3 significantly reduced the immobility times in FST and TST, demonstrating their antidepressant properties. The biomarkers study revealed that these compounds significantly enhanced hippocampus CAT, SOD and GSH, and reduced MDA levels in the scopolamine-induced stress mice model. These findings suggest the potential of curcumin analogues (C2 and C3) as antistress and antidepressant agents.

Comparison of interaction patterns of a triblock copolymer micelle with zwitterionic vs. cationic surfactant: An excited-state proton transfer dynamics investigation

This investigation explored the interaction between a triblock copolymer F127 (poly-(ethylene oxide)101 (PEO101)–poly(propylene oxide)56 (PPO56)–PEO101)) micelle and a zwitterionic sulfobetaine surfactant N-dodecyl-N, N-dimethyl-3-ammoniopropane sulfonate (SB3–12 or SB12), primarily utilizing the excited-state proton transfer (ESPT) dynamics of a photoacid, 8-hydroxy pyrene-1,3,6-trisulfonate (HPTS). We compared the obtained interaction pattern to that of the cationic surfactant, dodecyl trimethylammonium bromide (DTAB or C12TAB), with the same alkyl chains. The two surfactants, irrespective of charge differences, grossly follow the same pattern as manifested by the change in the intensity ratio of the protonated and deprotonated emission bands. For both cases, the ratio first increases above a specific surfactant concentration, attaining a maximum at a particular concentration. The ratio decreases at a high concentration and finally levels off at a very high concentration. Interestingly, the ratio attains maximum for a post-micellar (30–35 mM) concentration (~ 10 times higher than critical micellar concentration or CMC) for SB12 whereas, the maximum occurs at a sub-micellar (6–8 mM) concentration (significantly lower than its CMC) for DTAB. Detailed analysis of the time-dependent emission intensity ratio reveals that ESPT dynamics is slower in the optimum F127-SB12 assembly than in the case of the cationic surfactant. The fluorescence anisotropy decay of 8-methoxypyrene-1,3,6-trisulfonate (MPTS), a methoxy analog of HPTS, also corroborates well with the anomalous pattern; the rotational dynamics become more retarded inside the F127-SB12 assembly than in the case of the cationic surfactant. Thus, although SB12 requires a higher surfactant concentration to acquire the optimum state, it results in a more organized and less hydrated state than the cationic surfactant.

Structure-activity studies of PTPRD phosphatase inhibitors identify a 7-cyclopentymethoxy illudalic acid analog candidate for development

Interest in development of potent, selective inhibitors of the phosphatase from the receptor type protein tyrosine phosphatase PTPRD as antiaddiction agents is supported by human genetics, mouse models and studies of our lead compound PTPRD phosphatase inhibitor, 7-butoxy illudalic acid analog 1 (7-BIA). We now report structure–activity relationships for almost 70 7-BIA-related compounds and results that nominate a 7- cyclopentyl methoxy analog as a candidate for further development. While efforts to design 7-BIA analogs with substitutions for other parts failed to yield potent inhibitors of PTPRD’s phosphatase, ten 7-position substituted analogs displayed greater potency at PTPRD than 7-BIA. Several were more selective for PTPRD vs the receptor type protein tyrosine phosphatases S, F and J or the nonreceptor type protein tyrosine phosphatase N1 (PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B), phosphatases at which 7-BIA displays activity. In silico studies aided design of novel analogs. A 7-position cyclopentyl methoxy substituted 7-BIA analog termed NHB1109 displayed 600–700 nM potencies in inhibiting PTPRD and PTPRS, improved selectivity vs PTPRS, PTPRF, PTPRJ or PTPN1/PTP1B phosphatases, no substantial potency at other protein tyrosine phosphatases screened, no significant potency at any of the targets of clinically-useful drugs identified in EUROFINS screens and significant oral bioavailability. Oral doses up to 200 mg/kg were well tolerated by mice, though higher doses resulted in reduced weight and apparent ileus without clear organ histopathology. NHB1109 provides a good candidate to advance to in vivo studies in addiction paradigms and toward human use to reduce reward from addictive substances.

Photophysical characterization of a sub-micellar triblock copolymer-cationic surfactant aggregate for nanostructure synthesis

Surfactant assemblies are popular media for the synthesis of a variety of nanostructures. However, the use of excessive surfactants in these assemblies is detrimental to biological and medical applications. Herein, we optimized the size and interfacial packing of a sub-micellar aggregate of a triblock copolymer F127 (poly-(ethylene oxide)101 (EO101)−poly(propylene oxide)56 (PPO56)−PEO101), and several cationic alkyl trimethylammonium surfactants at minute concentrations and demonstrated its feasibility in synthesizing gold nano-triangles. We tracked various stages of the sub-micellar aggregate using an ultrasensitive photoacid 8-hydroxypyrene-1,3,6-trisulfonate (HPTS or Pyranine). The emission intensity (protonated/deprotonated) ratio of HPTS follows an intricate pattern against the surfactant concentration displaying three transition points (T1–3). The ratio starts to increase above an initial concentration (T1), attaining a maximum at an intermediate concentration (T2), and after that, decreases again before leveling off at a higher concentration (T3). Fluorescence anisotropy measurements of the methoxy analog 8-methoxypyrene-1,3,6-trisulfonate (MPTS) further revealed that the most organized state is near the critical point T2. Moreover, isothermal titration calorimetry (ITC) showed maximum enthalpy change at the same composition confirming optimum interaction. Finally, we show that the assemblies containing ultralow concentrations of both F127 and cationic surfactant can be a potent medium for synthesizing gold nano-triangles.

Synthesis, silver (I) extraction and silver (I) binding studies of novel N1,N3-bis(2-(benzylthio)ethyl)propanediamide derivatives

Solvent or liquid–liquid extraction represents a highly valuable technique for the selective recovery of metals from the aqueous phase due to the ease of operation and short turnaround times. Ligands bearing soft donor atoms including nitrogen and sulfur are ideal candidates for selective silver recovery due to their preference for silver binding. Herein, novel N1,N3-bis(2-(benzylthio)ethyl)propanediamide derivatives bearing sulfur and nitrogen donor atoms were prepared in low to high yields and tested for Ag+ extraction from ternary aqueous solutions also containing Cu2+ and Pb2+ following a well-established solvent extraction protocol. It was observed that electronics effects at the 4-aryl position in the propanediamide (or malondiamide) derivatives had a significant effect on the selectivity, but little effect on the efficiency of Ag+ extraction with the 4-methoxy analogue proving the most selective. Steric hindrance provided by dimethyl substitutions at the α-positions to the sulfur atoms had negative effects on Ag+ extraction efficiency and selectivity, while diethyl steric hindrance at the methylene center lowered selectivity but increased extraction efficiency for Ag+. Detailed binding studies reveal that one of the malondiamide derivatives which lacked the electronic and steric hindrance groups studied coordinated Ag+ in a 1:1 fashion suggesting a tetrahedral complex geometry. Overall, the results show that simple modification of the electronics and sterics of the N1,N3-bis(2-(benzylthio)ethyl)propanediamides, can improve their selectivity for Ag+ recovery from the aqueous phase.

Bis-7-hydroxy coumarinyl 1,2,3-triazole derived from benzimidazol-2-one as a water sensor: A fluorescence investigation

A click triazole derived from 4-azidomethyl-7-hydroxy-coumarin and 1,3-di(prop-2-ynyl)-1H-benzo[d]imidazol-2(3H)-one was found to exhibit ratiometric fluorescence response to water in DMF. Photophysical studies carried out for methoxy analogue of the title compound and analytical techniques employed in the study support involvement of water induced proton and photo induced electron transfer (PET) processes. Further, anion of the title compound generated in situ exhibited ‘turn off’ fluorescence for Fe3+, Cu2+, Hg2+ and Zn2+. PET on and off processes are also supported by DFT calculations.

Synthesis, physico-chemical properties and microsomal stability of compounds bearing aliphatic trifluoromethoxy group

Effects of the trifluoromethoxy substituent on physico-chemical properties of compounds, such as kinetic solubility, lipophilicity and microsomal clearance, was studied in a series of aliphatic derivatives. It was found that kinetic solubility of the CF3O-containing compounds was comparable to that of analogs, i.e. compounds bearing CH3O and CF3 moieties. The CF3O-substituted compounds had higher lipophilicity as compared to methoxy analogues, and nearly the same like CF3-bearing compounds. Microsomal stability studies indicated that the trifluoromethoxy group typically decreased metabolic stability of the corresponding derivatives as compared to either CH3O- or CF3-substituted counterparts, except for N-alkoxy(sulfon)amide series.

Substrate-Assisted Hydroxylation and O-Demethylation in the Peroxidase-like Cytochrome P450 Enzyme CYP121.

CYP121 is a P450 enzyme from Mycobacterium tuberculosis that catalyzes a C-C coupling reaction between the two aromatic rings on its native substrate cyclo(l-Tyr-l-Tyr) (cYY) to form mycocyclosin, a necessary product for cell survival. Unlike the typical P450 enzymes for hydroxylation, CYP121 is believed to behave like a peroxidase and conduct radical-mediated C-C bond formation. Here, we probe whether the phenolic hydrogen of the substrate is the site of the postulated hydrogen atom abstraction for radical formation. We synthesized a singly O-methylated substrate analogue, cYF-4-OMe, and characterized its interaction with CYP121 by ultraviolet-visible and electron paramagnetic resonance spectroscopies and X-ray crystallography. We found that cYF-4-OMe can function as a substrate of CYP121 using the established assay via the peroxide shunt. Analysis of the enzymatic reaction revealed an O-demethylation of cYF-4-OMe instead of cyclization, yielding cYY and formaldehyde. A hydroxylated substrate, cYF-4-OMeOH, is expected to be the intermediate product, which was trapped and structurally characterized by X-ray crystallography. We further determined that the deformylation reaction of cYF-4-OMeOH proceeds via an alkyl-oxygen rather than aryl-oxygen bond cleavage by the 18O-labeling studies. Finally, the pH dependence catalytic study on the native substrate and the methoxy analogue further supports the mechanistic understanding that the hydrogen atom abstraction is the critical first oxidation step exerted by a heme-based oxidant during the cyclization reaction of cYY. The switch in catalytic activity reveals the power of CYP121 as a P450 enzyme and provides insight into the peroxidase-like catalytic mechanism.

2-Phenylbenzoxazole derivatives as solid-state fluorescence emitters: Influence of steric hindrance and hydrogen bonding on the optical properties.

Six new 2-phenylbenzoxazole (PBO) derivatives, bearing either a methoxy or hydroxy group at position 5, were prepared via an efficient one-step synthesis that allowed both analogues to be obtained in equal proportions. These PBO derivatives also differed by the presence or absence of an alkyl substituent at the para-position of the phenyl group. In organic solutions, all six compounds were strongly fluorescent in the near-UV range. In the solid state, the 5-methoxy derivatives emitted bright light, ranging from violet to deep blue according to the substitution of the phenyl group. The presence of a bulky tert-butyl group indeed resulted in the separation of molecules, but also led to a deviation from molecular planarity. Remarkably, the introduction of a methyl group had a far more beneficial effect on the optical properties. With regard to the hydroxy derivatives, none of them was photoluminescent, probably due to strong intermolecular hydrogen bonding in the crystals. The 50:50 mixtures of methoxy and hydroxy analogues showed acceptable emission properties in the solid state. The substitution pattern also influenced the crystal habit of the pure compounds and the crystallinity of the mixtures. These cheap molecules could be adapted to suit a variety of applications in the field of photoluminescent materials.

Anomalous Variation of Excited-State Proton Transfer Dynamics inside a Triblock Copolymer-Cationic Surfactant Mixed Micelle.

Mixed micelles formed by triblock copolymers [poly(ethylene oxide)m (EOm)-poly(propylene oxide)n (POn)-EOm] with various surfactants have widespread applications. Molecular-level understanding of the composition, interfacial organization, and hydration of the copolymer-surfactant mixed micelle is greatly necessary from application perspectives. Here, we applied 8-hydroxypyrene-1,3,6-trisulfonate (HPTS) to probe the mixed micelle of a triblock copolymer F127 (EO101-PO56-EO101) and a cationic surfactant dodecyltrimethylammonium bromide (DTAB) at various compositions. The emission spectrum of HPTS modulates anomalously with the variation of DTAB concentration, displaying at least four regimes. The ratio of the emission intensities of the two bands (protonated/deprotonated) (1) first increases steeply in the low-concentration range (0.1-6 mM), (2) remains almost steady at the intermediate concentration (8-20 mM), (3) decreases at high concentration (20-80 mM), and (4) finally, remains almost constant at a very high concentration (100-400 mM) of DTAB. Time-resolved measurements confirm that excited-state proton transfer dynamics varies unusually with the concentration of DTAB in the mixed micelle; substantial retardation is observed up to ∼12 mM, but after that, the dynamics becomes somewhat faster upon further addition. The rotational dynamics of a methoxy analogue of HPTS, 8-methoxypyrene-1,3,6-trisulfonate, becomes slower up to ∼12 mM DTAB and after that becomes faster at higher concentration. Moreover, dynamic light scattering measurements showed that the size of the mixed micelle decreases sharply in the low-concentration region (<20 mM DTAB) but decreases moderately at high concentration. Thus, the nature of the mixed micelle is very different at low and high concentrations of DTAB. At low concentration, the incorporation of DTAB results in a more compact and less hydrated mixed micelle, whereas a more hydrated and less organized assembly is formed at high concentration of DTAB.

Radiosynthesis and in vivo evaluation of [11C]MOV as a PET imaging agent for COX-2

Radiosynthesis and in vivo evaluation of [11C]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (methoxy analogue of valdecoxib, [11C]MOV), a COX-2 inhibitor, was conducted in rat and baboon. Synthesis of the reference standard MOV (3), and its desmethyl precursor 2 for radiolabeling were performed using 1,2-diphenylethan-1-one as the starting material in five steps with 15% overall yield. Radiosynthesis of [11C]MOV was accomplished in 40 ± 10% yield and >99% radiochemical purity by reacting the precursor 2 in dimethyl formamide (DMF) with [11C]CH3I followed by removal of the dimethoxytrityl (DMT) protective group using trifluroacetic acid. PET studies in anesthetized baboon showed very low uptake and homogeneous distribution of [11C]MOV in brain. The radioligand underwent rapid metabolism in baboon plasma. MicroPET studies in male Sprague Dawley rats revealed [11C]MOV binding in lower thorax. The tracer binding in rats was partially blocked in heart and duodenum by the administration of 1 mg/kg oral dose of COX-2 inhibitor valdecoxib.

Correction: The Ketamine Analogue Methoxetamine and 3- and 4-Methoxy Analogues of Phencyclidine Are High Affinity and Selective Ligands for the Glutamate NMDA Receptor

[This corrects the article DOI: 10.1371/journal.pone.0059334.].

Substituent Modulation from ESIPT to ICT Emission in Benzoimidazolphenyl-methanones Derivatives: Synthesis, Photophysical and DFT Study

Design and synthesis of five new derivatives of benzophenone based imidazole dyes is presented. Synthesized dyes were well characterized by 1H NMR, 13C NMR, FT-IR and mass analysis. Dyes contain a secondary acceptor, ESIPT core and different donors forming (D-ESIPT core-A) as basic skeleton in order to study both ESIPT and ICT systematically in this same class of dyes. Dyes without a donor substituent showed ESIPT emission while dyes with a substituted strong donor showed intramolecular charge transfer (ICT) emission. Moreover emission properties of methoxy analogue dyes has been studied to further confirm non-ESIPT emission in dyes without donors and ICT emission in strong donor substituted dyes. All dyes exhibited long range emissions from 392 to 567 nm. Dyes exhibiting ESIPT emission showed negative solvatochromism while ICT emission exhibiting dyes shows positive solvatochromism. ICT and ESIPT characteristics are well correlated with polarity functions plots and Mulliken–Hush analysis. Experimental observations are well supported by TD–DFT and computed energies. The electrophilicity index has been calculated to get details of the stabilities of possible tautomers.

Total Synthesis and Antifungal Activity of Palmarumycin CP17 and Its Methoxy Analogues.

Total synthesis of naturally occurring spirobisnaphthalene palmarumycin CP17 and its methoxy analogues was first achieved through Friedel-Crafts acylation, Wolff-Kishner reduction, intramolecular cyclization, ketalization, benzylic oxidation, and demethylation using the inexpensive and readily available methoxybenzene, 1,2-dimethoxybenzene and 1,4-dimethoxybenzene and 1,8-dihydroxynaphthalene as raw materials. Demethylation with (CH3)3SiI at ambient temperature resulted in ring A aromatization and acetal cleavage to give rise to binaphthyl ethers. The antifungal activities of these spirobisnaphthalene derivatives were evaluated, and the results revealed that 5 and 9b exhibit EC50 values of 9.34 µg/mL and 12.35 µg/mL, respectively, against P. piricola.