Coumarin Compounds Research Articles

Chemical Constituents and Biological Activities of <i>Zanthoxylum limonella</i> (Rutaceae): A Review

Zanthoxylum limonella belongs to the family of aromatic deciduous trees and shrubs, Rutaceae. In traditional medicine practice, various parts of Z. limonella are used for the treatment of dental caries, febrifugal, sudorific, rheumatism, diuretic, stomach ache and diarrhea. Secondary metabolites have been isolated the stems, stem barks, and fruits. The plant contains alkaloid, amide, lignin, coumarin and terpenoid compounds. The extracts of the various parts, essential oil from the fruits and some pure compounds of Z. limonella have been found to have biological activities, for example, mosquito repellent and mosquito larvicidal, antimicrobial, antioxidant, and antitumour properties. This review compiles some scientific information on botanical description, traditional uses, phytochemical constituents and biological activities of Z. limonella.Keywords: Zanthoxylum limonella, Chemical constituents, Biological activities, Antimicrobial, Antioxidant, Antitumour

Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice.

Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2.

Design, Synthesis and Molecular Docking Study of 6,7-Dioxo-4-aryl-aminocoumarin

Catechol-O-methyltransferase (COMT) inhibitors play an important role in the treatment of Parkinson's disease (PD). On the basis of the structure-activity relation (SAR) analysis of existing COMT inhibitors, entacapone and tolcapone, it has been derived that coumarin compounds containing catechol structures may have inhibitory bioactivities on COMT. Thus, the novel COMT inhibitors, 6,7-dioxo-4-arylaminocoumarin compounds, were designed, and their inhibitory bioactivities on COMT were investigated by theoretical calculation. The results show that ten 6,7-dioxo-4-aryl-aminocoumarin compounds exhibit good docking effect, especially 6,7-bis(2-methoxyethoxy)-4-phenylamino-2H-chromen-2-one (6b4) and 4-(3-ethynylphenyl)amino-6,7-bis(2-methoxyethoxy)-2H-chromen-2-one (6b5) which have the structure of catechol protected by methoxy ethyl group.

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In the search for alternative ways to control Aedes aegypti with minimal environmental impact and in a manner that preserves human health, this study sought to evaluate the larvicidal effect of the invasive and antioxidant Spermacoce latifolia plant by performing a phytochemical study. Phytochemical screenings were done according to characterization reactions and thin layer chromatography. Phenolics compounds content (Folin-Ciocalteu's) and flavonoids (AlCl 3 ) spectrophotometric was performed, and the antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH). The phytochemical results revealed the presence of phenolic, flavonoid, tannin, steroid, free triterpene, coumarin, and alkaloid compounds. The content of total phenols (TPs) (482.7 ± 1.8 mg mgGA g -1 ) and flavonoids (165.4 ± 1.5 mg QE g -1 ) accounted for the antioxidant activity of 150 µg.mL -1 methanolic extract. In the proposed bioassays, groups of 25 third-stage larvae were challenged at different concentrations of plant crude extract (1.0, 0.5, 0.25, and 0.1 g L -1 ) of weight per volume in four replicates. In multiple concentration tests, the concentrations were selected to range from 0% to 100% mortality after 24 hours of contact with the solution. Toxicity was defined as the inhibition or total inactivity of the larvae. It was concluded that the methanol extract had an LC 50 of 0.62 g L -1 , indicating its potential use as a larvicide against A. aegypti and linking its activity to its phenolic and flavonoid components.

Cnidium monnieri: A Review of Traditional Uses, Phytochemical and Ethnopharmacological Properties.

Cnidium monnieri (L.) Cuss., an annual plant of the Umbelliferae species is one of the most widely used traditional herbal medicines and its fruits have been used to treat a variety of diseases in China, Vietnam, and Japan. The aim of this review is to provide an up-to-date and comprehensive analysis of the botany, traditional uses, phytochemistry, pharmacology, toxicity and contraindication of Cnidium monnieri (L.) Cuss. and to provide future directions of research on this plant. To date, 350 compounds have been isolated and identified from Cnidium monnieri (L.) Cuss., including the main active constituent, coumarins. In vitro and in vivo studies suggest that osthole and other coumarin compounds possess wide range of pharmacological properties for the treatment of female genitals, male impotence, frigidity, skin-related diseases, and exhibit strong antipruritic, anti-allergic, antidermatophytic, antibacterial, antifungal, anti-osteoporotic effects. Although coumarins have been identified as the main active constituents responsible for the observed pharmacological effects, the molecular mechanisms of their actions are still unknown. Therefore, further studies are still required to reveal the structure-activity relationship of these active constituents. In addition, toxicological and clinical studies are also required to provide further data for pharmaceutical use.

Effect of Cnidium Lactone on Serum Mutant P53 and BCL-2/BAX Expression in Human Prostate Cancer Cells PC-3 Tumor-Bearing BALB/C Nude Mouse Model.

BackgroundCnidium lactone is a natural coumarin compound that can inhibit a variety of cancer cell proliferation and induce cancer cell apoptosis. This experiment investigated the effect of cnidium lactone on molecular marker expression in prostate cancer nude mice to study its effect in inducing apoptosis.Material/MethodsWe randomly and equally divided 30 male BALB/C nude mice inoculated with human prostate cancer cells PC-3 into a negative control group, a cyclophosphamide group (500 mg/Kg), and cnidium lactone groups at 3 doses (280 mg/Kg, 140 mg/Kg, and 70 mg/Kg). The mice were weighed at 2 weeks after administration. Tunnel assay was applied to test the nude mice tumor cell apoptosis. ELISA was performed to detect serum AMACR, CD147, mutant P53, BCL-2, AND BAX expression levels. Tumor tissue was separated and weighed.ResultsMice weight did not change significantly in the groups receiving 3 different doses of cnidium lactone(p>0.05), while it decreased obviously in the cyclophosphamide group (p<0.05). Tumor weight, CD147, mutant P53, and BCL-2 levels were significantly lower in the groups receiving 3 different doses of cnidium lactone than in the negative control group (p<0.05). Among them, the abovementioned indexes decreased markedly in the 280 mg/Kg and 140 mg/Kg dose groups than in the cyclophosphamide group (p<0.05). AMACR and BAX levels showed no significant difference in the cnidium lactone group or the cyclophosphamide group (p>0.05).ConclusionsCnidium lactone may induce prostate cancer cell apoptosis and inhibit its proliferation through regulating CD147, mutant P53, and BCL-2 expression in nude mice.

In Vitro Assessment of Mutagenic And Genotoxic Effects of Coumarin Derivatives 6,7-Dihydroxycoumarin and 4-Methylesculetin

Coumarins are naturally occurring compounds, widely distributed throughout the plant kingdom (Plantae), and possess important pharmacological properties, including inhibition of oxidative stress. In this context, newly synthesized coumarin compounds are being produced due to their potent antioxidant activities. Therefore, the aim of the present study was to determine the in vitro cytotoxic, mutagenic, and genotoxic effects of 6,7-dihydroxycoumarin (6,7-HC) and 4-methylesculetin (4-ME) using the Salmonella/microsome test and in cultured human lymphocytes the comet assay and micronucleus test. The three coumarin derivatives concentrations evaluated in comet and MN assays were 2, 8, and 32 μg/mL, selected through a preliminary trypan blue-staining assay. In the Ames test, the 5 concentrations tested were 62.5, 125, 250, 500, and 750 μg/plate. Positive (methyl methane-sulfonate, MMS) and negative (dimethyl sulfoxide, DMSO) control groups were also included in the analysis. Our results showed that 4-ME induced greater cytotoxicity at high concentrations than 6,7-HC. In addition, both compounds were not mutagenic in the Ames test and not genotoxic or clastogenic/aneugenic in cultured human lymphocytes.

In Silico Investigation of a HIV-1 Vpr Inhibitor Binding Site: Potential for Virtual Screening and anti-HIV Drug Design.

Present HIV antiviral therapy only targets structural proteins of HIV, but evidence shows that the targeting of accessory proteins will expand our options in combating HIV. HIV-1 Vpr, a multifunctional accessory protein involved in viral infection, replication and pathogenesis, is a potential target. Previously, we have shown that phenyl coumarin compounds can inhibit the growth arrest activity of Vpr in host cells and predicted that the inhibitors' binding site is a hydrophobic pocket on Vpr. To investigate our prediction of the inhibitors' binding site, we docked the coumarin inhibitors into the predicted hydrophobic binding pocket on a built model of Vpr and observed a linear trend between their calculated binding energies and prior experimentally determined potencies. Subsequently, to analyze the inhibitor-protein binding interactions in detail, we built homology models of Vpr mutants and performed docking studies on these models too. The results revealed that structural changes on the binding pocket that were caused by the mutations affected inhibitor binding. Overall, this study showed that the binding energies of the docked molecules are good indicators of the activity of the inhibitors. Thus, the model can be used in virtual screening to identify other Vpr inhibitors and for designing more potent inhibitors.

Authentication of true cinnamon (Cinnamon verum) utilising direct analysis in real time (DART)-QToF-MS

The use of cinnamon as a spice and flavouring agent is widespread throughout the world. Many different species of plants are commonly referred to as ‘cinnamon’. ‘True cinnamon’ refers to the dried inner bark of Cinnamomum verum J. S. Presl (syn. C. zeylanicum) (Lauraceae). Other ‘cinnamon’ species, C. cassia (Nees & T. Nees) J. Presl (syn. C. aromaticum Nees) (Chinese cassia), C. loureiroi Nees (Saigon cassia), and C. burmannii (Nees & T. Nees) Blume (Indonesian cassia), commonly known as cassia, are also marketed as cinnamon. Since there is a prevalence of these various types of ‘cinnamons’ on the market, there is a need to develop a rapid technique that can readily differentiate between true cinnamon (C. verum) and other commonly marketed species. In the present study, coumarin and other marker compounds indicative of ‘cinnamon’ were analysed using DART-QToF-MS in various samples of cinnamon. This method involved the use of [M + H]+ ions in positive mode in addition to principal component analysis (PCA) using Mass Profiler Professional software to visualise several samples for quality and to discriminate ‘true cinnamon’ from other Cinnamomum species using the accurate mass capabilities of QToF-MS.

The Inhibitory Power Extract Of Balsamica Plant (Impatiens balsamica L) on Aeromonas hydrophila Bacteria Growth

This research aimed to assess the potential use of extracts of leaves, flowers, and stems of the balsamica plant increase inhibitory effect on the growth of Aeromonas hydrophila. The content of the plant contains a compound balsamica naphthoquinone, coumarin derivatives, tannins, flavonoids, and steroids. The active compounds have the ability as an antimicrobial. A hidrophyla bacteria, including opportunistic pathogens are almost always found in water and often cause disease when the fish in adverse conditions. Antibacterial activity test in this research using the spread plate method. Data obtained in the form of the extract, the results of bacterial inoculation, and the inhibition test results, will be analyzed, displayed with pictures and described descriptively. The result of the process of maceration extraction using ethanol 70% was obtained three extracts are concentrated leaf extract: 28.75 g, flower: 12.82 g, and rods: 29.48 g. The result of antibacterial extracts of leaves, stems, and flowers balsamica plant showed inhibitory activity on the A hydrophila bacteria that seems to be indicated by a clear zone around the paper disc. Based on the classification of leaf extract and extract of the stem can be classified in the class of strong, because the inhibition zone formed by the leaf extract is equal to 11.2 mm, and extract stem with 13.7 mm inhibition zone. Ability flower extract in inhibiting the growth of A hidrophila bacteria with 21.4 mm inhibition zone showed that the extract was included in a very strong class. Keywords: The ethanol extract balsamica, Impatiens balsamica L, Aeromonas hydrophila, antibacterial activity test.

Molecularly imprinted polymer for pre-concentration of esculetin from tobacco followed by the UPLC analysis

Molecularly imprinted polymers (MIPs) for solid-phase extraction and pre-concentration of esculetin have been successfully prepared by the bulk polymerization method using esculetin as a template molecule. Polymers of varying composition were prepared using different monomers (4-vinylpyridine, methacrylic acid, and acrylamide), ethylene glycol dimethacrylate as the cross-linker, 2,2-azobis(2-methylpropinitrile) as the initiator, and different porogen solvents (ethanol, acetone/methanol, and acetonitrile). The best polymer was obtained when 4-vinylpyridine was used as the monomer and acetone/methanol (3:2) as the porogen solvent, whereas the template:-monomer:-cross-linker ratio was 1:4:20. The imprinting factor of the selected MIPs for esculetin was 3.77. The polymers were evaluated according to their selective recognition properties for esculetin and structurally-related compounds (esculin, scopoletin, coumarin, and 7-methoxycoumarin). Chemical and morphological characterizations of the polymers were investigated by FTIR and scanning electron microscope, which confirmed a high degree of polymerization. Surface area, pore volume, and pore size of the polymer were investigated by Brunauer-Emmett-Teller analysis. MIPs were also successfully used as solid-phase adsorbent materials for the extraction of esculetin from tobacco leaves. Esculetin contents in dried tobacco leaves were found to be (9.27±0.17) μg g-1.

The influence of the extraction mode on three coumarin compounds yield from Prangos ferulacea (L.) Lindl roots

This study investigated the use of ultrasound-assisted extraction (USAE) to improve the extraction efficiency of the classical solvent extraction techniques such as maceration and Soxhlet extraction to extract three coumarin compounds (osthol, isoimperatorin and oxypeucedanin) from dried roots of Prangos ferulacea (L.) Lindl. Separation was accomplished on a reverse-phase C18 column with the mobile phase of methanol–water (70:30) and detection of the analytes was performed with UV variable detector at a wavelength of 322 nm. Under the optimum conditions, the extracted amounts of osthol, isoimperatorin and oxypeucedanin were 157.66, 172.54 and 79.27 mg g−1 dry herb, respectively. The results also indicated that compared with Soxhlet at 8 h and maceration extraction method at 3 days, ultrasound-assisted extraction increased the extraction yield of the total coumarin compounds about 17 and 31 %, respectively, at only 30 min. Therefore, USAE was preferred as the most efficient method which consumed less amount of a nontoxic solvent at a short time in comparison with conventional methods for extraction of coumarin compounds.

Esculetin suppresses lipopolysaccharide-induced inflammatory mediators and cytokines by inhibiting nuclear factor-κB translocation in RAW 264.7 macrophages.

Although previous studies have demonstrated that the natural coumarin compound esculetin possesses various pharmacological properties, the molecular mechanism of esculetin-mediated anti-inflammatory potential is not fully understood. In this study, we determined the effects of esculetin on lipopolysaccharide (LPS)-induced inflammatory responses of murine RAW 264.7 macrophages. The results indicate that esculetin inhibits LPS-induced nitric oxide and prostaglandin E2 production in a concentration-dependent manner, and inhibits inducible nitric oxide synthase and cyclooxygenase-2 expression in RAW 264.7 cells. Esculetin also significantly suppresses the production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, which was concomitant with a decrease in their expression levels. Furthermore, it was observed that esculetin attenuated the LPS-mediated nuclear factor-kappa B (NF-κB) translocation associated with the blocking of inhibitor of NF-κB (IκB)-α degradation as well as reactive oxygen species (ROS) production, without any significant cytotoxicity. These data suggest that, by blocking NF-κB activation, esculetin suppresses LPS-elicited inflammatory events, and this is mediated, at least in part, by inhibiting the generation of ROS. Collectively, these findings provide mechanistic insights into the anti-inflammatory action of esculetin in macrophages.

Esculetin (6,7-dihydroxycoumarin): a potential cancer chemopreventive agent through suppression of Sp1 in oral squamous cancer cells.

Esculetin (6,7-dihydroxycoumarin), a coumarin compound, is known to inhibit proliferation and induce apoptosis in several types of human cancer cells and is regarded as a promising chemotherapeutic agent. The purpose of the present study was to investigate the anti-proliferative effects of esculetin on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). We examined the apoptotic effects of esculetin were measured by MTS assay, DAPI staining, AnnexinV, PI staining, RT-PCR, western blot analysis and immunocytochemistry in HN22 and HSC4 cells. Taken together, the results of the present study indicate that esculetin had anti-proliferative effect on the growth of OSCC cells (HN22 and HSC4) in a dose- and time-dependent manner. The treatment of HN22 and HSC4 cells with esculetin led to a significant reduction in growth and induced apoptosis, followed by the regulation of Sp1 and Sp1 regulatory protein. This indicates that esculetin inhibited cell growth and induced apoptosis by suppressing Sp1 in HN22 and HSC4 cells, suggesting it to be a potent anticancer drug candidate for oral cancer.

Isolation and purification of psoralen and isopsoralen and their efficacy and safety in the treatment of osteosarcoma in nude rats.

Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans. To obtain coumarin compounds - psoralen and isopsoralen - from traditional Chinese medicine Psoralea corylifolia L. using chromatographic techniques and isolation and purification methods, and to observe the transplanted tumor growth inhibitory effects and adverse reactions of psoralen and isopsoralen in nude rats with osteosarcoma. Dried ripe fruits of Psoralea corylifolia L. were taken as the raw material to prepare crude extract of Psoralea corylifolia L. by ethanol reflux method. Column chromatography was used to isolate the crude extract; compounds were structurally identified based on (1)H-NMR, (13)C-NMR spectra, the two compounds were identified as psoralen andisopsoralen, and their contents were 99.7% and 99.6, respectively. Nude rat model of osteosarcoma was established; the rats were randomized into: normal saline group, psoralen low- and high-dose groups, isopsoralen low- and high-dose groups, and cisplatin group. Osteosarcoma volume and weight inhibition rates in nude rats in each group were observed; radioimmunoassay was used to determine the serum alkaline phosphatase activity; peripheral blood cell and bone marrow nucleated cell counts were determined; light microscopy was used to observe heart, liver, spleen, lung, kidney, and tumor histopathology; and electron microscopy was used to observe the fine structure of tumor cells. Tumor volume inhibition rates were 43.75% and 40.18%, respectively, in the psoralen and isopsoralen low-dose groups, and tumor weight inhibition rates were 38.83% and 37.77%. Tumor volume inhibition rates were 67.86% and 66.96%, respectively, in the psoralen and isopsoralen high-dose groups, and tumor weight inhibition rates were 49.47% and 47.87%. Psoralen and ispsoralen markedly lowered serum AKP level. Psoralen and isopsoralen induced apoptosis or necrosis of osteosarcoma. After administration of high doses of psoralen and isopsoralen, toxic reactions such as writhing, lassitude, and hypoactivity were seen. Kidney histopathology showed tubulointerstitial dilatation and congestion, and inflammatory cell aggregation in the renal intercellular space. Psoralen and isopsoralen did not cause any significant toxic side effects to the bone marrow, or other organs such as heart, lung, liver, and spleen. Psoralen and isopsoralen have growth inhibitory effects on transplanted tumor in nude rats with osteosarcoma, and can induce tumor cell apoptosis or necrosis, without significant toxic effects.

Functional traits of selected clones of southern sweet-grass (Hierochloë australis /Schrad./ Roem. &amp; Schult.)

Summary Southern sweet-grass (Hierochloë australis /Schrad./ Roem. &amp; Schult., Poaceae), commonly known as a bison grass, is a perennial tuft grass rarely occurring in mixed forests in Eastern and Northern Europe. The raw material collected from this plant are leaves rich in coumarin compounds (especially coumarin) responsible for sweet, specific aroma of these organs. In Poland, southern sweet-grass leaves are used mainly for alcohol products aromatisation. Growing demand for the raw material results in uncontrolled and excessive collecting of this plant. The best way to solve this problem is to introduce this plant into cultivation. Since southern sweet-grass is allogamous and heterozigotic, strong intraspecific variability of the species is observed. Fourteen clones of selected individuals from one population of southern sweet-grass naturally occurring in East Poland were compared in respect of morphological traits as well as accumulation of biologically active compounds. The clones differed significantly in the weight of leaves (3.76-22.59 g of air-dry weight per plant). The total coumarin content (determined by a spectrophotometric method) in this raw material for investigated clones ranged from 1.49 to 1.94%, flavonoids - from 0.25 to 0.55%, and phenolic acids - from 0.20 to 0.42%. Three coumarin compounds were identified by HPLC, namely coumarin, 3,4-dihydrocoumarin, and o-coumaric acid. The content of coumarin ranged from 84.00 to 310.85, 3,4-dihydrocoumarin: from 17.80 to 168.45, and o-coumaric acid: from 37.50 to 70.00 mg · 100 g-1 dry matter.

Design, synthesis, characterization, antioxidant and in vitro cytotoxic activities of novel coumarin thiazole derivatives

A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a–8d, 9) were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H NMR, 13C NMR and API-ES mass spectral data. In vitro evaluation of these coumarin compounds revealed cytotoxicity from 6.2 to 18 µg/mL against CEM, 8.2 to 21 µg/mL against L1210, 09 to 19 µg/mL against molt 4/C8, 8.6 to 12 µg/mL against HL60 and 8 to 16 µg/mL against BEL7402. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug ascorbic acid.

Antiplasmodial Evaluation of One Compound from &lt;i&gt;Calophyllum flavoranulum&lt;/i&gt;

Calophyllum flavoranulum (Clusiaceae family) is a big tree and medical plants from the tropical rain forest of the Indonesian continent. The organic extracts from stem bark yielded phenyl coumarin. The structure was elucidated with the aid of spectroscopic technique. Antiplasmodial activities of isolated compound was tested in vivo against Plasmodium berghei parasite and showed the best antiplasmodial activity. New flavoranulum coumarin compound showed activity against P. berghei parasite with inhibition growth 0, 31.33, 40, 30.67, 46 and 34% at dosage 1.1x10-10, 1.1x10-9, 1.1x10-8, 1.1x10-7, 1.1x10-6, and 1.1x10-5 mg/mL, respectively. Flavoranulum coumarin very active as antiplasmodial, and at 3 and 4 day incubation all of parasite were died.

Analysis of variation of coumarin and volatile compounds in Angelica Dahuricae Radix in different drying methods and conditions

To explore the effect of different processing methods and conditions of coumarin and volatile compounds in Angelica Dahuricae Radix and their change regularity, in order to optimize and establish appropriate drying methods and conditions. After being cleaned, fresh Angelica Dahuricae Radix herbs were baked, sun-dried, shade-dried, sun-dried after sulfur-fumigation, dried by quick-lime embedding, freeze-dried, microwave-dried. Finally, 24 groups of samples were obtained after being mashed and passing through the 60-mesh screen. The HPLC-PDA method was adopted to simultaneously determine the content of coumarin compounds. The GC-MS method was used to determine the content of volatile compounds. The principal component analysis (PCA) was made on the standardized analysis results for the 24 groups of samples processed with different drying methods. According to the PCA results, the comprehensive scores of coumarin and volatile compounds in Angelica Dahuricae Radix herbs processed with different methods in the order from high to low were that unpeeled and dried by quicklime embedding > unpeeled and dried with hot-air at 100 degrees C > unpeeled and dried with hot-air at 40 degrees C > peeled and infrared-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 40 degrees C > peeled and sun-dried > peeled and dried with hot-air at 60 degrees C > peeled and dried with hot-air at 100 degrees C > peeled and microwave-dried > peeled and dried with hot-air at 80 degrees C > unpeeled and sun-dried > unpeeled and dried with sulfur-fumigation > peeled and dried with sulfur-fumigation > unpeeled and dried with hot-air at 120 degrees C > unpeeled and freeze-dried > unpeeled and infrared-dried > peeled and dried with hot-air at 120 degrees C > peeled and freeze-dried > peeled and dried by quicklime embedding > unpeeled and dried with hot-air at 80 degrees C > peeled and shade-dried > unpeeled and shade-dried > unpeeled and microwave-dried. According to the findings, different drying processing methods have certain impacts on the content coumarin and volatile compounds in Angelica Dahuricae Radix herbs. The traditional method of drying by quicklime embedding is recommended as the optimum origin processing method of Angelica Dahuricae Radix, which is followed by the method for being peeled and dried with hot-air at 100 degrees C.

Monte Carlo Method Based QSAR Modeling of Coumarin Derivates as Potent HIV‐1 Integrase Inhibitors and Molecular Docking Studies of Selected 4‐phenyl Hydroxycoumarins

Summary In search for new and promising coumarin compounds as HIV-1 integrase inhibitors, chemoinformatic methods like quantitative structure-activity relationships (QSAR) modeling and molecular docking have an important role since they can predict desired activity and propose molecule binding to enzyme. The aim of this study was building of QSAR models for coumarin derivatives as HIV-1 integrase inhibitors with the application of Monte Carlo method. SMILES notation was used to represent the molecular structure and for defining optimal SMILES-based descriptors. Molecular docking into rigid enzyme active site with flexible molecule was performed. Computational results indicated that this approach can satisfactorily predict the desired activity with very good statistical significance. For best built model statistical parameters were: a) 3’ Processing activity: R2=0.9980 and Q2=0.9977 for training set and R2=0.9788 for test set and b) Integration activity: R2=0.9999 and Q2=0.9998 for training set and R2= 0.9213 for test set. Built QSAR models were applied to selected 4-phenyl hydroxycoumarins for calculating desired activity and for HIV-1 integrase inhibition estimation. Additionally, molecular docking study was performed to a newly identified pocket in the HIV-1 integrase enzyme structure for determination of selected 4-phenyl hydroxycoumarins binding mode. Monte Carlo method proved to be an efficient approach to build up a robust model for estimating HIV-1 integrase inhibition of coumarin compounds. Based on QSAR and molecular docking studies, 4-phenyl hydroxycoumarins can be considered as promising model compounds for developing new HIV-1 integrase inhibitors.