Grewiifopenes A-K, bioactive clerodane diterpenoids from Casearia grewiifolia Vent.

Eleven novel clerodane-type diterpenoids, grewiifopenes A-K (1-4 and 12-18), along with nine known compounds (5-11, 19, and 20) were purified from the dichloromethane extract of the twigs and stems of Casearia grewiifolia Vent. (Salicaceae). Their spectroscopic data, including the NMR, HRESIMS, and electronic circular dichroism calculations were employed to completely characterize and elucidate the chemical structures and absolute configurations. The clerodane diterpenoids possessing a 6-OH group and no substitution at C-7 exhibited greater cytotoxic activity than others, with their IC50 values ranging from 0.3 to 2.9 µM. Isocaseamembrin E (7) exhibited antibacterial activity against Staphylococcus aureus, while isocaseamembrin E (7), corymbulosin X (8), caseargrewiin A (9), kurzipene A (10), and balanspene F (11) exhibited antibacterial activity against Bacillus cereus.

Dual-functional natural rubber latex foam composites for solar-driven clean water production and heavy metal decontamination.

Solar steam generation (SSG) offers a sustainable approach to fresh water production. Herein, a novel dual-functional natural rubber/carbon black composite foam evaporator is presented for a cost-efficient SSG system that both produces fresh water and eliminates heavy metals present in the water. The composite foam is produced using the Dunlop process, and in its optimized form, it absorbed >96 % of sunlight. The foam evaporator exhibited a thermal conductivity of 0.052 W/m⋅K, a water evaporation rate of 1.40 kg/m2/h, converted 83.38 % of light to heat under 1 sun irradiation, and showed outstanding stability. The technology required to produce this composite foam is already available to make large-scale production feasible, while the natural raw materials are abundant. On the basis of its performance qualities, the rubber foam composite appears to be an excellent candidate for application as a viable solar absorber for SSG to produce fresh, clean water for commercial purposes.

Albiflorenes A-L, polyoxygenated cyclohex(a/e)ne diterpene esters from Kaempferia albiflora.

Twelve polyoxygenated cyclohex(a/e)ne diterpene esters, named albiflorenes A-L (1-12), were isolated from the whole plants of Kaempferia albiflora, known as "Prao Mang Mum." Their structures and relative stereochemistry were determined by extensive spectroscopic analysis. Furthermore, the comparison of experimental electronic circular dichroism (ECD) curves with the curves predicted by TDDFT was used to determine the absolute configurations. Albiflorenes contain polyoxygenated cyclohexane (or cyclohexene) derivatives, which are linked to either isopimarane or abietane diterpene acid units. The discovery marks the first occurrence of a conjugate between polyoxygenated cyclohexane (or cyclohexene) rings and diterpenoids. Among the isolates, albiflorene C specifically exhibited antibacterial activity against Bacillus cereus with MIC and MBC values of 3.13 and 6.25 µg/mL, respectively.

Green magnetic carbon/alginate biocomposite beads from iron scrap waste for efficient removal of textile dye and heavy metal.

The circular economy can help enhance the value of industrial waste and remediate the environment. This study considers the application of iron scrap from steel production as a free resource to produce magnetic adsorbent beads to remove methylene blue dye and lead (II) ions from wastewater. Composite beads were prepared by incorporating iron scrap and activated carbon into a calcium alginate gel using a simple 'mix and drop' synthesis. The optimized magnetic beads were stable and offered a large specific surface area. The maximum adsorption capacity of the adsorbent, calculated from the Langmuir isotherm model, was 476.19 mg g-1 for methylene blue and 163.93 mg g-1 for lead (II) ions. This study places emphasis upon the zero-waste principle and employs a scalable synthetic approach for the conversion of waste iron scrap into an adsorbent material capable of delivering significant environmental benefits.

Synthesis, Antiacetylcholinesterase Activity, and Molecular Dynamics Simulation of Aporphine-benzylpyridinium Conjugates.

A series of aporphines conjugated with an N-benzylpyridinium moiety through an amide-bond linkage were synthesized and evaluated for their acetylcholinesterase (AChE) inhibitory activity. The conjugation of the N-benzylpyridinium group significantly enhanced the AChE inhibitory activity of the core aporphine. The halogen substituents on the benzyl group affected the activity of the conjugates. Both (S)- and (R)-enantiomers of three conjugates with low IC50 values were synthesized and evaluated for their activities. All (S)-enantiomers exhibited higher activity than the corresponding (R)-enantiomers. The (S)-enantiomer of 2-chlorobenzylpyridinium-containing aporphine was the most potent inhibitor in this study with an IC50 value of 0.06 ± 0.003 µM. Molecular dynamics simulation analysis revealed that both enantiomers can interact with the AChE binding site, whereas the (S)-enantiomer possessed slightly stronger interaction than the (R)-enantiomer, presumably because of their different orientations, as evidenced by molecular docking. The N-benzylpyridinium dehydroaporphine conjugates were also synthesized but were less active than the corresponding aporphine conjugates.

Influence of a Transparent and Edible Coating of Encapsulated Cannabidiol Nanoparticles on the Quality and Shelf Life of Strawberries.

Cannabidiol (CBD) has been shown to have antioxidant and antibacterial effects. The investigation into CBD's potential as an antioxidant and antibacterial agent, meanwhile, is still in its initial stages. The study goals were to prepare encapsulated cannabidiol isolate (eCBDi), evaluate the effect of eCBDi edible active coatings on the physicochemical properties of strawberries, and determine whether CBD and sodium alginate coatings could be used as a postharvest treatment to promote antioxidation and antimicrobial activity and prolong the strawberry shelf life. A well-designed edible coating on the strawberry surface was achieved using eCBDi nanoparticles in combination with a sodium alginate polysaccharide-based solution. Strawberries were examined for their visual appearance and quality parameters. In the results, a significantly delayed deterioration was observed in terms of weight loss, total acidity, pH, microbial activity, and antioxidant activity for coated strawberries compared to the control. This study demonstrates the capability of eCBDi nanoparticles as an efficient active food coating agent.

Turmeric Herb Extract-Incorporated Biopolymer Dressings with Beneficial Antibacterial, Antioxidant and Anti-Inflammatory Properties for Wound Healing.

Bacterial infection and inflammation caused by excess oxidative stress are serious challenges in chronic wound healing. The aim of this work is to investigate a wound dressing based on natural- and biowaste-derived biopolymers loaded with an herb extract that demonstrates antibacterial, antioxidant, and anti-inflammatory activities without using additional synthetic drugs. Turmeric extract-loaded carboxymethyl cellulose/silk sericin dressings were produced by esterification crosslinking with citric acid followed by freeze-drying to achieve an interconnected porous structure, sufficient mechanical properties, and hydrogel formation in situ in contact with an aqueous solution. The dressings exhibited inhibitory effects on the growth of bacterial strains that were related to the controlled release of the turmeric extract. The dressings provided antioxidant activity as a result of the radical scavenging effect on DPPH, ABTS, and FRAP radicals. To confirm their anti-inflammatory effects, the inhibition of nitric oxide production in activated RAW 264.7 macrophages was investigated. The findings suggested that the dressings could be a potential candidate for wound healing.

Acetylcholinesterase modified inkjet-printed graphene/gold nanoparticle/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) hybrid electrode for ultrasensitive chlorpyrifos detection.

This study successfully created a portable acetylcholinesterase sensor on a printed hybrid electrode capable of detecting chlorpyrifos in the field. While a screen-printed electrode was chosen herein to enable a single-use and portable platform for the in-field application, the hybrid material was incorporated to ensure ultrasensitive detection at lower electrode potentials. The hybrid ink of gold nanoparticles (AuNPs) decorated on graphene (GP) sheets in poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) was synthesized through a simple completely-green one-pot process. The subsequent characterization was carried out via transmission electron microscopy (TEM), X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier-transform infrared spectroscopy (FTIR). The synergy resulting from the greater surface area and enhanced transfer of electrons combined with high levels of electrocatalytic activity and superb conductivity offered by GP, AuNP, and PEDOT:PSS allows the sensor to exhibit ultrasensitive chlorpyrifos detection at the relatively low detection limit of 0.07 nM. The sensor demonstrated in this study also exhibits good reproducibility, desirable stability, and a successful application for the real sample with satisfactory recovery results of around 106 %, indicating its potential for use as a tool in the analysis of pesticides.

Allicin and Capsaicin Ameliorated Hypercholesterolemia by Upregulating LDLR and Downregulating PCSK9 Expression in HepG2 Cells.

Hypercholesterolemia is a common cause of cardiovascular diseases (CVDs). Although allicin and capsaicin possess hypolipidemic effects through several molecular mechanisms, their effects on LDLR and PCSK9 expression are still unknown. This study aimed to investigate the effects of allicin and capsaicin on LDLR and PCSK9 expression in HepG2 cells. The effects of allicin and capsaicin on cell viability were evaluated by MTT assay and trypan blue exclusion assay. Low-density lipoprotein receptor (LDLR) levels and LDL uptake were determined by flow cytometry and confocal laser scanning microscopy (CLSM), respectively. RT-qPCR and Western blot analyses were performed to evaluate the expression of PCSK9, LDLR, SREBP-2, and HNF1α. ELISA was used to measure PCSK9 levels in culture media. Allicin and capsaicin increased the protein expression levels of LDLR via activation of the transcription factor SREBP2. However, allicin and capsaicin decreased the expression of PCSK9 protein and the secretion of PCSK9 in culture media via the suppression of HNF1α. Moreover, allicin and capsaicin increased LDL uptake into HepG2 cells. The efficacies of the hypolipidemic effects of allicin (200 µM) and capsaicin (200 µM) were comparable to that of atorvastatin (10 µM) in this study. In conclusion, allicin and capsaicin possessed hypolipidemic effects via the upregulation of LDLR and downregulation of PCSK9 expression, thereby enhancing LDL uptake into HepG2 cells. This indicates that allicin and capsaicin should be used as potent supplements to ameliorate hypercholesterolemia.

Quercetin/Hydroxypropyl-ß-Cyclodextrin Inclusion Complex-Loaded Hydrogels for Accelerated Wound Healing.

This study concentrated on developing quercetin/cyclodextrin inclusion complex-loaded polyvinyl alcohol (PVA) hydrogel for enhanced stability and solubility. Quercetin was encapsulated in hydroxypropyl-ß-cyclodextrin (HP-ß-CD) by the solvent evaporation method. The prepared quercetin/HP-ß-CD inclusion complex showed 90.50 ± 1.84% encapsulation efficiency (%EE) and 4.67 ± 0.13% loading capacity (%LC), and its successful encapsulation was confirmed by FT-IR and XRD. The quercetin/HP-ß-CD inclusion complex was well dispersed in viscous solutions of PVA in various amounts (0.5, 1.0, 1.5. 2.5, and 5.0% w/v ratio), and the drug-loaded polymer solution was physically crosslinked by multiple freeze-thaw cycles to form the hydrogel. The cumulative amount of quercetin released from the prepared hydrogels increased with increasing concentrations of the inclusion complex. The introduction of the inclusion complex into the PVA hydrogels had no influence on their swelling ratio, but gelation and compressive strength reduced with increasing inclusion complex concentration. The potential cytotoxicity of quercetin/HP-ß-CD inclusion complex hydrogels was evaluated by MTT assay and expressed as % cell viability. The results show biocompatibility toward NCTC 929 clone cells. The inhibitory efficacy was evaluated with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay, and the results show a higher level of antioxidant activity for quercetin/HP-ß-CD inclusion complex hydrogels compared with free quercetin. The findings of our study indicate that the developed quercetin/HP-ß-CD inclusion complex hydrogels possess the required properties and can be proposed as a quercetin delivery system for wound-healing applications.

One-Pot and Green Preparation of Phyllanthus emblica Extract/Silver Nanoparticles/Polyvinylpyrrolidone Spray-On Dressing.

A spray-on wound dressing has many benefits, including easy and quick administration to broad and uneven wounds, better interface with the wound site, adhesion without additional dressing, and multiple applications in a portable package. By limiting direct contact with the wound site, such a design can prevent wound damage during treatment. This study revealed a simple, one-pot synthesis of spray-on wound dressing relying on polyvinylpyrrolidone solution incorporating silver nanoparticles as a broad-spectrum antibacterial agent and wound-healing antioxidant Phyllanthus emblica extract. Silver nanoparticles were synthesized in situ using Phyllanthus emblica extract as a biogenic reducing agent. Polyvinylpyrrolidone was employed as a film-forming agent to create an adhesive hydrogel-based dressing matrix to provide moisture and establish a shielding barrier for the wound bed as well as to regulate the release of fruit extract. In vitro tests revealed that the produced dressing film had a controlled release of the fruit extract, high antioxidant activity, and a good antibacterial action against S. aureus, P. aeruginosa, E. coli, and MRSA. Additionally, a biocompatibility study has shown that both human fibroblasts and keratinocytes are unaffected by the dressing film. Based on established findings, the current spray-on solution might be a potential option for antibacterial wound dressing.

Diterpenoids and p-methoxycinnamic acid diol esters from Kaempferia saraburiensis Picheans. (Zingiberaceae): Structural assignment of saraburol and their biological activities.

Five undescribed compounds, including three diterpenoids namely, saraburol, saraburanes A and B, and two p-methoxycinnamic acid monoterpene diol esters, named E/Z-saraburinic esters, together with ten known oxygenated isopimarane diterpenoids, were isolated from the whole plant of Kaempferia saraburiensis Picheans. Among these compounds, saraburol possesses an unusual 6/9/6 tricyclic ring system bearing a 1,3-dioxonane-4-one scaffold, which is rarely found in natural products. The structure of isolated compounds was elucidated by spectroscopic methods, including HRESIMS, FTIR, 1D and 2D-NMR, and by comparison with published data, and their absolute configurations were determined by comparison of experimental with calculated ECD spectra and hydrolysis reaction. Using gauge-independent atomic orbital (GIAO) NMR shift calculations coupled with DP4+ probability analyses, biogenetic considerations, and optical rotation allowed for the complete characterization of saraburol. A plausible biosynthetic pathway for saraburol and saraburane A was proposed. The cytotoxicity result indicated that E-saraburinic ester exhibited the most potent activity with an IC50 value of 12.0 µM against MOLT-3 cells with a selectivity index of 12.5. Saraburane B exhibited the most potent activity against Gram-positive bacteria strain Staphylococcus epidermidis with MIC (MBC) value of 25 (50) µg/mL.

Computational Screening of Phenylamino-Phenoxy-Quinoline Derivatives against the Main Protease of SARS-CoV-2 Using Molecular Docking and the ONIOM Method.

In the search for new anti-HIV-1 agents, two forms of phenylamino-phenoxy-quinoline derivatives have been synthesized, namely, 2-phenylamino-4-phenoxy-quinoline and 6-phenylamino-4-phenoxy-quinoline. In this study, the binding interactions of phenylamino-phenoxy-quinoline derivatives and six commercially available drugs (hydroxychloroquine, ritonavir, remdesivir, S-217622, N3, and PF-07321332) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease (Mpro) were investigated using molecular docking and the ONIOM method. The molecular docking showed the hydrogen bonding and hydrophobic interactions of all the compounds in the pocket of SARS-CoV-2 main protease (Mpro), which plays an important role for the division and proliferation of the virus into the cell. The binding free energy values between the ligands and Mpro ranged from -7.06 to -10.61 kcal/mol. The molecular docking and ONIOM results suggested that 4-(2',6'-dimethyl-4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline and 4-(4'-cyanophenoxy)-2-(4″-cyanophenyl)-aminoquinoline have low binding energy values and appropriate molecular properties; moreover, both compounds could bind to Mpro via hydrogen bonding and Pi-Pi stacking interactions with amino acid residues, namely, HIS41, GLU166, and GLN192. These amino acids are related to the proteolytic cleavage process of the catalytic triad mechanisms. Therefore, this study provides important information for further studies on synthetic quinoline derivatives as antiviral candidates in the treatment of SARS-CoV-2.

Structural Basis of 2-Phenylamino-4-phenoxyquinoline Derivatives as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors.

New target molecules, namely, 2-phenylamino-4-phenoxyquinoline derivatives, were designed using a molecular hybridization approach, which was accomplished by fusing the pharmacophore structures of three currently available drugs: nevirapine, efavirenz, and rilpivirine. The discovery of disubstituted quinoline indicated that the pyridinylamino substituent at the 2-position of quinoline plays an important role in its inhibitory activity against HIV-1 RT. The highly potent HIV-1 RT inhibitors, namely, 4-(2',6'-dimethyl-4'-formylphenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6b) and 4-(2',6'-dimethyl-4'-cyanophenoxy)-2-(5″-cyanopyridin-2″ylamino)quinoline (6d) exhibited half-maximal inhibitory concentrations (IC50) of 1.93 and 1.22 µM, respectively, which are similar to that of nevirapine (IC50 = 1.05 µM). The molecular docking results for these two compounds showed that both compounds interacted with Lys101, His235, and Pro236 residues through hydrogen bonding and interacted with Tyr188, Trp229, and Tyr318 residues through π-π stacking in HIV-1 RT. Interestingly, 6b was highly cytotoxic against MOLT-3 (acute lymphoblastic leukemia), HeLA (cervical carcinoma), and HL-60 (promyeloblast) cells with IC50 values of 12.7 ± 1.1, 25.7 ± 0.8, and 20.5 ± 2.1 µM, respectively. However, 6b and 6d had very low and no cytotoxicity, respectively, to-ward normal embryonic lung (MRC-5) cells. Therefore, the synthesis and biological evaluation of 2-phenylamino-4-phenoxyquinoline derivatives can serve as an excellent basis for the development of highly effective anti-HIV-1 and anticancer agents in the near future.

Injectable eggshell-derived hydroxyapatite-incorporated fibroin-alginate composite hydrogel for bone tissue engineering.

Tissue engineering is a promising approach to repair and regenerate damaged or lost tissues or organs. In dental aspect, reconstruction of the resorbed alveolar bone after tooth extraction plays an important role in the success of dental substitution, especially in dental implant treatment. The hydroxyapatite (HA)-incorporated fibroin-alginate composite injectable hydrogel was fabricated to be used as scaffold for bone regeneration. HA was synthesized from eggshell biowaste. Fibroin was extracted from Bombyx mori cocoon. The synthesized HA, fibroin and alginate hydrogel were characterized. HA-incorporated fibroin-alginate hydrogel had decreased pore size and porosity compared with pure alginate hydrogel. Thermal analysis showed that hydrogel had a degradation peak of approximately 250 °C. Hydrogel could absorb water, with a swelling ratio of around 300% at 24 h. Hydrogel was degraded as time passed and almost completely degraded at day 7. Its compressive Young's modulus was approximately 0.04 ± 0.02 N/mm2 to 0.10 ± 0.02 N/mm2. Primary cytotoxicity test indicated non-toxic potential of the fabricated hydrogel. Increased ALP activity was observed in MC3T3-E1 cultured in HA-incorporated fibroin-alginate hydrogel. Results suggested the potential use of injectable HA fibroin-alginate hydrogel as dental scaffolding material. Further studies including in vivo examinations are needed prior to its clinical application.

Zingiber cassumunar Roxb. Essential Oil-Loaded Electrospun Poly(lactic acid)/Poly(ethylene oxide) Fiber Blend Membrane for Antibacterial Wound Dressing Application.

The essential oil from Zingiber cassumunar Roxb. (Plai) has long been used in Thai herbal remedies to treat inflammation, pains, sprains, and wounds. It was therefore loaded into an electrospun fibrous membrane for use as an analgesic and antibacterial dressing for wound care. The polymer blend between poly(lactic acid) and poly(ethylene oxide) was selected as the material of choice because its wettability can be easily tuned by changing the blend ratio. Increasing the hydrophilicity and water uptake ability of the material while retaining its structural integrity and porosity provides moisture balance and removes excess exudates, thereby promoting wound healing. The effect of the blend ratio on the fiber morphology and wettability was investigated using scanning electron microscopy (SEM) and contact angle measurement, respectively. The structural determination of the prepared membranes was conducted using Fourier-transform infrared spectroscopy (FTIR). The release behavior of (E)-1-(3,4-dimethoxyphenyl) butadiene (DMPBD), a marker molecule with potent anti-inflammatory activity from the fiber blend, showed a controlled release characteristic. The essential oil-loaded electrospun membrane also showed antibacterial activity against S. aureus and E. coli. It also exhibited no toxicity to both human fibroblast and keratinocyte cells, suggesting that the prepared material is suitable for wound dressing application.

Magnetic carbon nanofiber composite adsorbent through green in-situ conversion of bacterial cellulose for highly efficient removal of bisphenol A.

A magnetic carbon nanofiber sorbent was facilely synthesized from bio-based bacterial cellulose and FeCl3via impregnation, freeze-drying, followed by pyrolysis at 700 °C, without additional activation or nanofiber fabrication. The obtained material possessed intrinsic 3D naturally fibrous and porous structure with good magnetization. The adsorption results showed that the adsorption capacity of the prepared adsorbent towards bisphenol A (BPA) was as high as 618 mg/g, outperforming other adsorbents. Moreover, recycling the adsorbent for 10 consecutive cycles retained 96% of initial adsorption efficiency. The magnetic sorbent can maintain good magnetic properties even with recycling. Hence, the use of bacterial cellulose as a renewable carbon nanofiber precursor and FeCl3 as a source of magnetic particles, and a green pore generating agent in the present protocol, lead to a superior magnetic carbon nanofiber adsorbent with sustainable characteristics.

Preparation of chitosan/hydrolyzed collagen/hyaluronic acid based hydrogel composite with caffeic acid addition.

In this work, biopolymer hydrogels were synthesized by mixing hyaluronic acid, hydrolyzed collagen, and chitosan through a solvent evaporation method and incorporating them with caffeic acid as an antioxidant agent. The obtained caffeic acid-loaded chitosan/hydrolyzed collagen/hyaluronic acid hydrogels were characterized by X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. No significant change on structural and thermal properties was observed. Furthermore, scanning electron microscope reported that the surface morphology of the hydrogels was smooth, and no significant change in porosity was observed after the addition of hyaluronic acid. With high amount of hyaluronic acid, the swelling behaviour was superiority. The hydrogels showed an initial burst release of caffeic acid (~70%) within 60 min, followed by a gradual release of up to 80% by 480 min. The release was slightly higher with the presence of hyaluronic acid. In addition, DPPH, ABTS+, and FRAP assays revealed that the caffeic acid-loaded hyaluronic acid/hydrolyzed collagen/chitosan hydrogels exhibited antioxidant activity. Thus, these composites could potentially be used as dressing materials with antioxidant activity.

Binding interaction of potent HIV-1 NNRTIs, amino-oxy-diarylquinoline with the transport protein using spectroscopic and molecular docking.

In the present investigation, the intermolecular interaction of 4-(4'-cyanophenoxy)-2-(4''-cyanophenyl)-aminoquinoline (1), a potent non-nucleoside HIV-1 reverse transcriptase inhibitors, with the transport proteins, namely bovine serum albumin (BSA) and human serum albumin (HSA), has been investigated under physiological conditions employing UV-Vis, fluorescence spectrophotometry, competitive binding experiments and molecular docking methods. The results indicated that binding of (1) to the transport proteins caused fluorescence quenching though a static quenching mechanism. The number of binding site (n) and the apparent binding constant (Kb) between (1) and the transport proteins were determined to be about 1 and 104-105 L·mol-1 (at three different temperatures; 298, 308, 318 K), respectively. The interaction of (1) upon binding to the transport proteins was spontaneous. The enthalpic change (ΔH°) and the entropic change (ΔS°) were calculated to be -56.50 kJ·mol-1, -72.31 J·mol-1 K-1 for (1)/BSA, respectively and computed to be -49.35 kJ·mol-1, -58.64 J·mol-1 K-1, respectively for (1)/HSA, respectively. The results implied that the process of interaction force of (1) with the transport protein were Vander Waals force and/or hydrogen bonding interactions. The site maker competitive experiments revealed that the binding site of (1) with the transport proteins were mainly located within site I (sub-domain IIA) in both proteins. Additionally, the molecular docking experiment supported the above results which confirmed the binding interaction between (1) and the transport proteins. This study will come up with basic data for explicating the binding mechanisms of (1) with the transport protein and can be great significance in the opening to clarify the transport process of (1) in vivo.

Molecular Docking Studies and Synthesis of Amino-oxy-diarylquinoline Derivatives as Potent Non-nucleoside HIV-1 Reverse Transcriptase Inhibitors.

In this study, amino-oxy-diarylquinolines were designed using structure-guided molecular hybridization strategy and fusing of the pharmacophore templates of nevirapine (NVP), efavirenz (EFV), etravirine (ETV, TMC125) and rilpivirine (RPV, TMC278). The anti-HIV-1 reverse transcriptase (RT) activity was evaluated using standard ELISA method, and the cytotoxic activity was performed using MTT and XTT assays. The primary bioassay results indicated that 2-amino-4-oxy-diarylquinolines possess moderate inhibitory properties against HIV-1 RT. Molecular docking results showed that 2-amino-4-oxy-diarylquinolines 8(A-D): interacted with the Lys101 and His235 residue though hydrogen bonding and interacted with Tyr318 residue though π-π stacking in HIV-1 RT. Furthermore, 8A: and 8D: were the most potent anti-HIV agents among the designed and synthesized compounds, and their inhibition rates were 34.0% and 39.7% at 1 µM concentration. Interestingly, 8A: was highly cytotoxicity against MOLT-3 (acute lymphoblastic leukemia), with an IC50 of 4.63±0.62 µg/mL, which was similar with that in EFV and TMC278 (IC50 7.76±0.37 and 1.57±0.20 µg/ml, respectively). Therefore, these analogs of the synthesized compounds can serve as excellent bases for the development of new anti-HIV-1 agents in the near future.