Methoxy Derivatives Research Articles

Aerobic bacterial degradation of polychlorinated biphenyls and their hydroxy and methoxy derivatives

Polychlorinated biphenyls are persistent organic pollutants hazardous to humans and to the environment. The products of biotransformation of these compounds can exist in natural objects as hydroxy and methoxy derivatives. This review summarizes the biodegradation pathways of polychlorinated biphenyls under the action of aerobic bacterial strains. The possibility of complete biodegradation of polychlorinated biphenyls and their derivatives under laboratory conditions is demonstrated. This information is valuable for researchers specializing in the biotransformations and toxicity of polychloroarene derivatives and would be useful for the development of remediation processes of natural objects contaminated with polychlorinated biphenyls.<br> The bibliography includes 253 references.

Aromatic Difluoroboron β-Ketoiminate Complexes: Effect of Substituents on Mechanofluorochromism and Polymorphic Behavior.

Aromatic difluoroboron β-ketoiminate complexes (ketimBF2) are structural nitrogen-containing analogues of aromatic difluoroboron β-diketonates (diketBF2). Aggregation-induced emission (AIE) and polymorphic behavior allow ketimBF2 to exhibit mechanofluorochromic (MFC) properties. A detailed comparative study of the luminescence of a wide range of ketimBF2 with H- and CH3-substituents of nitrogen atom and diketBF2 with various substituents of the chelate ring (methyl, phenyl, toluoyl, anisoyl, biphenyl, naphthyl, anthracyl) in the solid state was carried out. As a result, regularities of the influence of substituents on the luminescent and MFC properties for 21 dyes have been established. Replacing one oxygen atom in diketBF2 with nitrogen atom in the chelate ring (H-substituted ketimBF2) changes the nature of the molecular stacking in crystals, which is manifested in different MFC properties. The introduction of a methyl group into the chelate ring (CH3-substituted ketimBF2) induces steric hindrance, which prevents the efficient formation of supramolecular structures and, consequently, leads to the shortest-wavelength monomeric emission in the solid state in comparison with oxygen and H-substituted nitrogen analogues. Methoxy derivative of H-substituted ketimBF2 exhibits non-reversible fluorochromic switching after annealing and can be used as temperature indicator to control unauthorized heating of temperature-sensitive substances during transportation and storage.

6-Substituted benzo[d]thiazole linked 2-(2-(bis (1H-benzo[d]imidazol-2-yl) methylene) hydrazineyl compounds: Synthesis, computational studies, and in-vitro anticancer assessment

In this study, four novel 6-substituted benzothiazole-linked bis-benzimidazoles (3a–d) were synthesized and characterized using 1H NMR, 13C NMR, FTIR, and HRMS techniques. The physicochemical properties of these compounds were examined, and experimental data validated the computed values. The absorption and emission properties were also investigated using carbonate, acetate, and phosphate buffers at various pH levels.In-silico studies revealed that methoxy derivative (3c) possesses the highest docking affinity for tyrosine kinase. Pharmacokinetic studies showed that, like the marketed drug erlotinib, none of the compounds act as substrates for p-glycoprotein, and all except compound 3d do not inhibit CYP-2C9. The gastrointestinal absorption profiles, including blood-brain barrier permeability, were also studied. Drug-likeness assessments based on Lipinski's rule of five and Ghose criteria suggested favourable properties, though some compounds showed deviations in molecular weight and logP values. In-vitro anticancer study via MTT assay includes its potency against MCF-7 and MDA-MB-231 breast cancer cell lines, including 3c as the most potent against MCF-7 cells, which coincides with the In-silico study.

Photochemical method for preparation of benzo[a]pyrano[3,2‐c]phenazin‐4‐ones from quinoxalines with 4‐pyranone unit

AbstractPhotochemical properties of terarylenes with quinoxalines bridge unit and allomaltol fragment was investigated. We have demonstrated that starting compounds with hydroxyl group in 3‐hydroxy‐4‐pyranone substituent does not undergo any photoinduced transformations. Wherein, conversion to methoxy derivatives allows one to realize photochemical 6π‐electrocyclization for considered quinoxalines. Based on data of x‐ray analysis the observed difference in reactivity is connected with the presence of hydrogen bond in hydroxyl derivatives. As a result of carried out research photochemical approach to novel benzo[a]pyrano[3,2‐c]phenazin‐4‐ones was implemented.

Mucolytic Drugs Ambroxol and Bromhexine: Transformation under Aqueous Chlorination Conditions.

Bromhexine and ambroxol are among the mucolytic drugs most widely used to treat acute and chronic respiratory diseases. Entering the municipal wastewater and undergoing transformations during disinfection with active chlorine, these compounds can produce nitrogen- and bromine-containing disinfection by-products (DBPs) that are dangerous for aquatic ecosystems. In the present study, primary and deep degradation products of ambroxol and bromhexine obtained in model aquatic chlorination experiments were studied via the combination of high-performance liquid and gas chromatography with high-resolution mass spectrometry. It was shown that at the initial stages, the reactions of cyclization, hydroxylation, chlorination, electrophilic ipso-substitution of bromine atoms with chlorine, and oxidative N-dealkylation occur. Along with known metabolites, a number of novel primary DBPs were tentatively identified based on their elemental compositions and tandem mass spectra. Deep degradation of bromhexine and ambroxol gives twenty-four identified volatile and semi-volatile compounds of six classes, among which trihalomethanes account for more than 50%. The specific class of bromhexine- and ambroxol-related DBPs are bromine-containing haloanilines. Seven of them, including methoxy derivatives, were first discovered in the present study. One more novel class of DBPs associated with bromhexine and ambroxol is represented by halogenated indazoles formed through dealkylation of the primary transformation products containing pyrazoline or tetrahydropyrimidine cycle in their structure.

Small phenolic compounds as potential endocrine disruptors interacting with estrogen receptor alpha.

The human body is regularly exposed to simple catechols and small phenols originating from our diet or as a consequence of exposure to various industrial products. Several biological properties have been associated with these compounds such as antioxidant, anti-inflammatory, or antiplatelet activity. Less explored is their potential impact on the endocrine system, in particular through interaction with the alpha isoform of the estrogen receptor (ERα). In this study, human breast cancer cell line MCF-7/S0.5 was employed to investigate the effects on ERα of 22 closely chemically related compounds (15 catechols and 7 phenols and their methoxy derivatives), to which humans are widely exposed. ERα targets genes ESR1 (ERα) and TFF1, both on mRNA and protein level, were chosen to study the effect of the tested compounds on the mentioned receptor. A total of 7 compounds seemed to impact mRNA and protein expression similarly to estradiol (E2). The direct interaction of the most active compounds with the ERα ligand binding domain (LBD) was further tested in cell-free experiments using the recombinant form of the LBD, and 4-chloropyrocatechol was shown to behave like E2 with about 1/3 of the potency of E2. Our results provide evidence that some of these compounds can be considered potential endocrine disruptors interacting with ERα.

4‐substituted push‐pull quinazoline chromophores with extended π‐conjugated linker

AbstractA series of four push‐pull compounds based on a 4‐phenylquinazoline scaffold were designed. Three of these compounds exhibit dual state emission with intense fluorescence in solution and solid state. Their emission properties are sensible to environement stimuli with intense emission solvatochromism and halochromism. In case of methoxy derivative, both neutral and protonated form are luminescent and white light emission can be observed by controlled partial protonation.

Аналитические реакции 2,4-динитрофенилгидразина с некоторыми альдегидами в мицеллах катионных ПАВ

The analytical effect of micelles of cationic surfactants in the reactions of some aromatic aldehydes (AA) with 2,4-dinitrophenylhydrazine (DNPH) with the formation of the corresponding aci-forms of hydrazones has been established. It has been established that micelles of nonionic and anionic surfactants do not cause analytically significant effects in the system under study. Analytical characteristics of systems DNPH–AA– cationic surfactant (molar absorption coefficients (ε), ranges of determined contents, limits of detection) were determined, using the example of benzaldehyde and its nitro-, sulfo-, chlorine-, dimethylamino- and methoxy derivatives, as well as p-dime thylaminocinnamic aldehyde (DMAC). For the majority of aldehydes ranges of determined contents are in the range from 0,2 to 2,1 μg/ml, ε from 2.10-4 to 1.10-5 L.mol-1.cm-1. The hydrazone formed by DNPH and DMAC was synthesized and identified by elemental analysis and IR spectroscopically. The solubility of the resulting hydrazone in aqueous (pH 13) and micellar (cetylpyridinium chloride, CPC) media was studied. It has been shown that its solubility in CPC micelles increases approximately 60 times, which leads to the stabilization of the studied system DNPH – AA – cationic surfactant in time (its isotropy) and an increase in the sensitivity of the determination of the corresponding aldehyde in the absence of volatile and toxic organic solvents, while the principle “green chemistry” has been implemented. The established effect of cationic surfactants was implemented to develop a method for the non-extraction photometric determination of streptomycin (a broad-spectrum aminoglycoside antibiotic effective against tuberculosis) in pharmaceutical preparations with ranges of determined contents from 2,1 to 87,4 μg/ml. The error of direct photometric determination of streptomycin did not exceed 5–9%.

Steroidogenic activity of liposomal methylated resveratrol analog 3,4,5,4′-tetramethoxystilbene (DMU-212) in human luteinized granulosa cells in a primary three-dimensional in vitro model

PurposeSteroid hormone secretion is one of the key functions of granulosa cells (GCs). Resveratrol is a natural polyphenol, known for its beneficial health effects, such as improving reproductive health. However, its application is limited due to poor bioavailability. The methoxy derivative of resveratrol (DMU-212) was demonstrated to be more lipophilic, and therefore of greater bioavailability. However, since the addition of methoxy groups to the stilbene scaffold was found to make the molecule insoluble in water, DMU-212 was loaded into liposomes. This study aimed to evaluate how the liposomal formulation of DMU-212 (lipDMU-212) alters estradiol and progesterone secretion of human ovarian GCs in a primary three-dimensional cell culture model.MethodsDMU-212-loaded liposomes were prepared by thin film hydration followed by extrusion. Cell viability was measured after exposure of GCs spheroids to the liposomal formulation of DMU-212 using CellTiter-Glo® 3D Cell Viability Assay. The secretion of estradiol and progesterone was determined using commercial ELISA kits. RT-qPCR was conducted to analyze the expression of steroidogenesis-related genes. Finally, the western blot technique was used to analyze the effect of lipDMU-212 and FSH treatments on CYP11A1 and HSD3B1 protein levels.ResultslipDMU-212 was found to significantly increase estradiol and progesterone secretion in a dose-dependent manner by enhancing the expression of CYP11A1, HSD3B1, StAR, CYP17A1, CYP19A1, and HSD17B1 genes. We have also shown that lipDMU-212, used alone and in combination with FSH, significantly increased the expression of the HSD3B1 and CYP11A1 proteins in GCs. Furthermore, our study suggests that lipDMU-212 increases FSH activity.ConclusionsThis is the first study to describe the steroidogenic activity of liposomal formulation of DMU-212, possibly through increasing the StAR and CYP19A1 expression. These findings suggest that lipDMU-212 might have a beneficial effect in the treatment of disorders related to estrogen deficiency and hyperandrogenism, such as PCOS.

Synthesis and Biological Evaluation of Resveratrol Methoxy Derivatives.

Resveratrol, a naturally occurring stilbene, exhibits numerous beneficial health effects. Various studies have demonstrated its diverse biological actions, including anti-oxidant, anti-inflammatory, and anti-platelet properties, thereby supporting its potential for cardio protection, neuroprotection, and anti-cancer activity. However, a significant limitation of resveratrol is its weak bioavailability. To overcome this challenge, multiple research groups have investigated the synthesis of new resveratrol derivatives to enhance bioavailability and pharmacological activities. Nevertheless, there are limited data on the effects of resveratrol derivatives on platelet function. Therefore, the objective of this study was to synthesize resveratrol methoxy derivatives and evaluate their anti-platelet and anti-proliferative activity. Platelet-rich plasma (PRP) obtained from healthy volunteers was utilized to assess the derivatives' ability to inhibit platelet aggregation induced by platelet activating factor (PAF), adenosine diphosphate (ADP), and thrombin receptor activating peptide (TRAP). Additionally, the derivatives' anti-tumor activity was evaluated against the proliferation of PC-3 and HCT116 cells. The results revealed that some methoxy derivatives of resveratrol exhibited comparable or even superior anti-platelet activity compared to the original compound. The most potent derivative was the 4'-methoxy derivative, which demonstrated approximately 2.5 orders of magnitude higher anti-platelet activity against TRAP-induced platelet aggregation, indicating its potential as an anti-platelet agent. Concerning in silico studies, the 4'-methyl group of 4'-methoxy derivative is oriented similarly to the fluorophenyl-pyridyl group of Vorapaxar, buried in a hydrophobic cavity. In terms of their anti-tumor activity, 3-MRESV exhibited the highest potency in PC-3 cells, while 3,4'-DMRESV and TMRESV showed the greatest efficacy in HCT116 cells. In conclusion, methoxy derivatives of resveratrol possess similar or improved anti-platelet and anti-cancer effects, thereby holding potential as bioactive compounds in various pathological conditions.

Biological Evaluation and Binding Mechanism of 5-HT7 Specific Arylpiperazinyl-Alkyl Benzothiazolone: Radiobiology and Photo-physical Studies.

Diversely substituted methoxy derivatives of arylpiperazinyl-alkyl benzothiazolone has been evaluated as specific probe for 5HT7. To determine the best methoxy derivative for 5HT7 receptor affinity, we synthesised a number of 2-benzothiazolone arylalkyl piperazine derivatives. In-vitro/vivo studies with C-2 substituted [11C]ABT showed 5HT7 specific binding. The radiochemical purity of [11C]ABT was found to be more than 99% with radiochemical stability persistence for more than 1.5 hr at 25 °C. The interaction of BSA and ABT has been analysed by photophysical studies for better understanding of properties such as adsortion, distribution, metabolism and elemination (ADME). The interaction between ABT and BSA was analyzed by using the UV-vis and fluorescence spectra. UV-vis spectra analyzed the changes in primary structure of BSA on its interaction with ABT. ABT showed quenched fluorescence emission intensity of tryptophan residues in BSA via static quenching mechanism. This study might help to understand how ABT binds to serum protein or subsequently to know the ADME of this drug candidate.

Novel Tetrahydro-[1,2,4]triazolo[3,4-a]isoquinoline Chalcones Suppress Breast Carcinoma through Cell Cycle Arrests and Apoptosis.

Chalcones are interesting anticancer drug candidates which have attracted much interest due to their unique structure and their extensive biological activity. Various functional modifications in chalcones have been reported, along with their pharmacological properties. In the current study, novel chalcone derivatives with the chemical base of tetrahydro-[1,2,4]triazolo[3,4-a]isoquinolin-3-yl)-3-arylprop-2-en-1-one were synthesized, and the structure of their molecules was confirmed through NMR spectroscopy. The antitumor activity of these newly synthesized chalcone derivatives was tested on mouse (Luc-4T1) and human (MDA-MB-231) breast cancer cell lines. The antiproliferative effect was evaluated through SRB screening and the MTT assay after 48 h of treatment at different concentrations. Interestingly, among the tested chalcone derivatives, chalcone analogues with a methoxy group were found to have significant anticancer activity and displayed gradient-dependent inhibition against breast cancer cell proliferation. The anticancer properties of these unique analogues were examined further by cytometric analysis of the cell cycle, quantitative PCR, and the caspases-Glo 3/7 assay. Chalcone methoxy derivatives showed the capability of cell cycle arrest and increased Bax/Bcl2 mRNA ratios as well as caspases 3/7 activity. The molecular docking analysis suggests that these chalcone methoxy derivatives may inhibit anti-apoptotic proteins, particularly cIAP1, BCL2, and EGFRK proteins. In conclusion, our findings confirm that chalcone methoxy derivatives could be considered to be potent drug candidates against breast cancer.

N1-aryl-2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-one as convenient platform to design high photostable and long-lived dyad fluorophore with potential application in live-cell imaging

The design of long-lived and high photostable fluorescent probes with high quantum yields (QYs) is of great significance for biological applications. It favors the monitoring of individual molecular events for extended period of time without side-effect consequences into cell. From a series of N1-aryl-2-(trifluoromethyl)benzo[b][1,8]naphthyridin-4(1H)-ones, we found that their photophysical properties were successfully tuned through the modulation of the intramolecular charge-transfer (ICT), generating the largest lifetimes, highest QYs and photostability for those fluorophores with a high CT character. The ICT was primarily controlled by incorporation of methoxy group at 7-position and secondarily by electron-deficient N1-arene at 1-position of benzo[b] [1,8] naphthyridin-4(1H)-one core. The trifluoromethyl at 2-position seems to strength the ICT because it reduced gap energies and increase dipole moments in their derivatives compared to 2-methyl or -hydrogen analogues. Importantly, from the 7-methoxy derivatives, two high photo-stable (15- to 17-fold more than fluorescein) and long-lived (9.75–14.20 ns) fluorophores with acceptable QYs and HOMO-LUMOs were identified. In particular, the fluorophore 3k showed a low cytotoxicity in J774.1A macrophage, pH insensibility and appropriate lipophilicity, which in combination with their good photophysical properties favored the application of the 7-methoxy dyes for bioimaging, giving blue-fluorescent macrophages in relatively short time. Then, the N1-aryl-2-(trifluoromethyl)benzo[b] [1,8] naphthyridin-4(1H)-one by its molecular extension and planarity emerges as an interesting platform to generate long-lived and highly photostable dyes and, the key point is to favor the strength of the internal ICT mechanism through the incorporation of appropriate donor (D) and acceptor (A) groups along the D-A chain.

Non-oxidative photoreaction of 1,3,5-triaryl-2-pyrazoline-4-ol (4-methoxy) derivatives

• A suitable procedure for the synthesis of 2-pyrazoline-4-ol (-methoxy) derivatives is proposed. • Non-oxidative photochemical reaction of 2-pyrazoline-4-ol (-methoxy) derivatives in CHCl 3 is occurred. • The electronic nature of the substituent on the 4- and 5-positions on the photochemical behavior is studied. • An efficient mechanism for the electron-transfer induced photoelimination reaction in chloroform is proposed. • DFT computational studies (optimization, orbital contour maps, MEP, NBO) at the B3LYP/6-31++(d,p) level of theory on these compoundsare reported. A series of 4-hydroxy- or 4-methoxy-substituted 1,3,5-triaryl-2-pyrazolines were synthesized and their structures, especially trans -orientation of 4- and 5-hydrogens of the 2-pyrazoline ring were characterized by analysis of IR, 1 H NMR, 13 C NMR spectra as well as the single-crystal structure study. In order to elucidate the effect of 4-hydroxy- or 4-methoxy-substitution on the photochemical behavior of these compounds, they were exposed to the UV light. The results explain the occurrence of a non-oxidative photoreaction, by the expulsion of 4-substitution and elimination of a molecule of water or methanol under the formation of the aromatized pyrazole ring. Density functional theory (DFT) calculations were carried out to support the proposed electron-transfer induced photoreaction mechanism. Natural bond orbital (NBO) analysis explains the preferred electron detachment process from the N 1 -atom rather than the oxygen atom of the hydroxy or the methoxy groups. Proton detachment from the involved radical cation species leads to the formation of the radical intermediate centered at the C 5 -position of the heterocyclic ring. Elimination of the hydroxy or the methoxy group accomplished the photoreaction under the formation of the C 4 -unsubstituted pyrazole molecule.

Anti-inflammatory and Analgesic Studies of 2-aryl-3-(5-alkyl-1, 3, 4-thiadiazol-2-yl) 4-thiazolidinones

Any damage and bad stimulus causes pain and inflammation. The compound used for pain is known as analgesic and for inflammation is known as anti-inflammatory. The title compounds were evaluated for analgesic activity using Tail-Flick method and anti-inflammatory activity using Carrgenan Induced Rat Paw Edema. Diclofenac Sodium used as standard drug. The chloro, fluro and nitro containg derivatives showed best activity as compared to methyl, methoxy and hydroxy derivatives.

Methoxy and methylthio-substituted trans-stilbene derivatives as CYP1B1 inhibitors – QSAR study with detailed interpretation of molecular descriptors

A quantitative structure–activity relationship (QSAR) model was built using multiple linear regression (MLR) to predict the ability of series methyl and/or methylthio trans -stilbene derivatives to inhibit CYP1B1. Twenty-four compounds with their activity expressed as the negative log of the IC 50 value (pIC50 [M]) were split into a training (20 compounds) and a test set (four compounds) using Kennard and Stone algorithm. Molecular descriptors were calculated using alvaDesc software after compound optimization in the Gaussian 09 package in PL-Grid. The model characterized by the best validation parameters (R 2 TRAIN = 0.954, Q 2 LOO = 0.898, R 2 TEST = 0.880) was chosen based on the chemometric method – cluster analysis. The applicability domain has been determined, indicating that the regression model can give reliable prediction. The study shows that the inhibitory activity against CYP1B1 of the methyl and/or methylthio trans -stilbene derivatives can be predicted by RDF035m, Mor10m, Eig04_AEA(bo), RDF070s, MaxDD descriptors. Finally, the paper attempts to interpret three-dimensional descriptors by assessing the impact of interatomic interactions, following the partition of molecules into fragments, on the final value of descriptors.

Theoretical calculations of formation and reactivity of o-quinomethide derivatives of resorcin[4]arene with reference to empirical data.

This paper describes theoretical reaction pathways of alkoxybenzyl derivatives of resorcin[4]arene leading to the formation of o-quinomethide derivatives of resorcin[4]arene (o-QMR[4]A). For each case, the activation energies for the formation of one o-QMR[4]A unit and the activation energies for the backward reaction were calculated. Based on the calculated reaction pathways, the reaction mechanism of o-QMR[4]A formation was proposed. Using the example of o-QMR[4]A generated from a methoxy derivative of resorcin[4]arene, the activation energies with selected nucleophiles were calculated and the reaction mechanisms discussed. Reaction path calculations were performed using the nudged elastic band method and semiempirical extended tight-binding method (GFN2-xTB). Using hydroxybenzyl derivatives of resorcin[4]arene as an example, a comparison of calculated activation energies by selected density-functional theory methods with GFN2-xTB and B97-3c geometries was performed. B97-3c and wB97XD methods were used to calculate the energies of the reactants (R), transition states (TS) and products (P) of the analysed reactions. Theoretical reaction mechanisms were discussed with respect to the orbital-weighted Fukui dual descriptor (Δfw) and experimental data.

Isothermal Titration Calorimetry for Characterizing the Zinc(II)‐Binding Properties of Photocaged Complexes with Micromolar Affinity

AbstractMorphDeCage (2‐(4‐methoxy‐3‐nitrophenyl)‐2‐morpholinoacetic acid) and PyrDeCage (2‐(4‐methoxy‐3‐nitrophenyl)‐2‐(methyl(pyridin‐2‐ylmethyl)amino)acetic) are Zn2+ photocages that utilize photodecarboxylation of the methoxy derivative of meta‐nitrophenylacetic acid as the release mechanism. Isothermal titration calorimetry (ITC) was used an alternative to usual approaches to measure the Zn2+ binding affinities of these new compounds owing to unsuccessful measurement by competitive titration with 4‐(2‐pyridylazo)resorcinol (PAR). MorphDeCage forms a 1 : 1 ligand‐metal complex with a 106 μM Kd value. PyrDeCage forms both a 1 : 1 and 1 : 2 metal: ligand complexes with 3.2 and 21.7 μM Kd values respectively. To further demonstrate the efficacy of the ITC methodology and provide a comparison to direct UV‐vis titrations data, two photocages based on Sanger's reagent (SRPs) were prepared. The Kd values of the SRPs measured by UV‐vis titration and ITC were internally consistent and support the retraction of the original report (J. Am. Chem. Soc. 2020, 142, 3806–3813), which was withdrawn due to errors in binding affinity measurements.

Characterization and separation of wood tar by full temperature range fractional distillation

Wood tar has been regarded as the most undesirable by-product of biomass carbonization. Fractional distillation of the wood tar at the full temperature range from the initial evaporating point to the coking point (110∼300 °C), was investigated. Characterization of the six typical distillates in the wood tar in terms of moisture content, elemental and chemical compositions was precisely analyzed to evaluate the effectiveness of the distillation process in separating the components. A life cycle assessment based on biomass converting to wood tar and further into distilled-oils was constructed to estimate the CO2 emission. Results showed high yields (∼15.4 wt%) of the heavy distillates (b.p. 250∼300 °C) and a significant reduction in water content (∼4.5 %) while high heating value (∼30 MJ/kg). The majority of the compounds presented in each fraction is phenolic, aromatic and oxygenated compounds especially phenols and their alkyl and methoxy derivatives. Phenolic compounds perform various distillation properties due to different functional groups and the hydrogen-bond interaction. LCA indicated that the distillation exerted advantages in reducing carbon emission and that it has a potential for future development of these processes for commercial and industrial use.

Synthesis and anti-influenza virus activity evaluation of novel andrographolide derivatives

In this paper, using AI78-38, an andrographolide analog with novel skeleton, as the lead compound, we designed and synthesized fifteen amide derivatives at the 17 position of AI78-38. In the synthesis of key intermediate IM4, the low yield of the SeO2 oxidation step impeded the further study. Aiming at improving the yield, White reagent was applied to furnish IM4 by catalyzing the allylic C–H oxidation at the 7, 8, 17 position. It is also firstly reported that White reagent possessed the ability of oxidating the cyclic substrates. Compared with SeO2 oxidative approach, the modified synthetic method utilized by White reagent increased the yield from 32.0 to 53.6%. The anti-influenza A virus (H3N2) results showed that 4-methoxy derivative 10 offered the greatest inhibitory ability, with an IC50 value of 90.2 μg/ml, slightly more potent than ribavirin. Furthermore, the drug-likeness and ADMET properties of compound 10 and AI78-38 were evaluated using the Discovery Studio 2.1 software and the online SwissADME. The results showed that compound 10 offered good bioavailability and overcame the disadvantages of the ADMET properties in AI78-38. Graphical abstract