Displaying publications 1 - 20 of 27 in total

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  1. Alleviatory effects of Danshen, Salvianolic acid A and Salvianolic acid B on PC12 neuronal cells and Drosophila melanogaster model of Alzheimer's disease
    Tan FHP, Ting ACJ, Leow BG, Najimudin N, Watanabe N, Azzam G
    J Ethnopharmacol, 2021 Oct 28;279:114389.
    PMID: 34217797 DOI: 10.1016/j.jep.2021.114389
    ETHNOPHARMACOLOGICAL RELEVANCE: Danshen water extract (DWE), obtained from the Salvia miltiorrhiza Bunge (Family Lamiaceae) root, is usually employed in Chinese traditional medicine as treatment to cardiovascular ailments and cerebrovascular diseases. Intriguingly, the extract was also found to contain vast beneficial properties in Alzheimer's disease (AD) treatment.

    AIM OF THE STUDY: Alzheimer's disease is the most significant type of neurodegenerative disorder plaguing societies globally. Its pathogenesis encompasses the hallmark aggregation of amyloid-beta (Aβ). Of all the Aβ oligomers formed in the brain, Aβ42 is the most toxic and aggressive. Despite this, the mechanism behind this disease remains elusive. In this study, DWE, and its major components, Salvianolic acid A (SalA) and Salvianolic acid B (SalB) were tested for their abilities to attenuate Aβ42's toxic effects.

    METHODS: The composition of DWE was determined via Ultra-Performance Liquid Chromatography (UPLC). DWE, SalA and SalB were first verified for their capability to diminish Aβ42 fibrillation using an in vitro activity assay. Since Aβ42 aggregation results in neuronal degeneration, the potential Aβ42 inhibitors were next evaluated on Aβ42-exposed PC12 neuronal cells. The Drosophila melanogaster AD model was then employed to determine the effects of DWE, SalA and SalB.

    RESULTS: DWE, SalA and SalB were shown to be able to reduce fibrillation of Aβ42. When tested on PC12 neuronal cells, DWE, SalA and SalB ameliorated cells from cell death associated with Aβ42 exposure. Next, DWE and its components were tested on the Drosophila melanogaster AD model and their rescue effects were further characterized. The UPLC analysis showed that SalA and SalB were present in the brains and bodies of Drosophila after DWE feeding. When human Aβ42 was expressed, the AD Drosophila exhibited degenerated eye structures known as the rough eye phenotype (REP), reduced lifespan and deteriorated locomotor ability. Administration of DWE, SalA and SalB partially reverted the REP, increased the age of AD Drosophila and improved most of the mobility of AD Drosophila.

    CONCLUSION: Collectively, DWE and its components may have therapeutic potential for AD patients and possibly other forms of brain diseases.

    Matched MeSH terms: Benzofurans/pharmacology*
  2. Atmospheric PCDDs/PCDFs levels and occurrences in Southeast Asia: A review
    Zain SMSM, Latif MT, Baharudin NH, Anual ZF, Mohd Hanif N, Khan MF
    Sci Total Environ, 2021 Aug 20;783:146929.
    PMID: 34088111 DOI: 10.1016/j.scitotenv.2021.146929
    Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are toxic compounds derived from anthropogenic sources that stay in the environment for long periods. Ambient air has become the most important pathway for the transfer of PCDDs/PCDFs from emission sources to the environment. This review intends to summarise the information available on atmospheric PCDDs/PCDFs in the countries of Southeast Asia to provide a detailed description of the trends in PCDDs/PCDFs emissions, key sources, and levels in urban, rural, and industrial air as reported in peer-reviewed literature since 2000 and by the United Nations Environment Programme. As the largest country in Southeast Asia, Indonesia is the major PCDDs/PCDFs emitter, accounting for 72.81% of the total release of PCDDs/PCDFs in the air from all available inventories in this region, while Brunei Darussalam is the lowest emitter, contributing to less than 0.02%. Open burning processes have become the largest source of ambient PCDDs/PCDFs in the region (69.62%), followed by waste incineration (10.69%), and ferrous and non-ferrous metal production (8.78%). PCDDs/PCDFs levels in rural areas ranged between 10 and 38 fg TEQ m-3; however, where open burning waste has occurred, the levels rose to 12-29 times higher. In urban areas, ambient levels were 15 times greater than in rural areas, varying from 23 to 565 fg TEQ m-3. Atmospheric concentrations near industrial palm oil and waste incinerator sites were between 64 and 1530 fg TEQ m-3. The non-cancer risk of ambient exposure to PCDDs/PCDFs through inhalation is low among populations near facilities emitting PCDDs/PCDFs. The lack of local technical capacity, the high economic costs, and the lack of established human resource capacities have been the major challenges in conducting ambient PCDDs/PCDFs studies in most countries in the region.
    Matched MeSH terms: Benzofurans; Dibenzofurans, Polychlorinated
  3. Fulltext A novel Diels-Alder adduct of mulberry leaves exerts anticancer effect through autophagy-mediated cell death
    Shu YH, Yuan HH, Xu MT, Hong YT, Gao CC, Wu ZP, et al.
    Acta Pharmacol Sin, 2021 May;42(5):780-790.
    PMID: 32814819 DOI: 10.1038/s41401-020-0492-5
    Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.
    Matched MeSH terms: Benzofurans/pharmacology; Benzofurans/therapeutic use*
  4. Fulltext Synthesis, in vitro urease inhibitory potential and molecular docking study of benzofuran-based-thiazoldinone analogues
    Taha M, Rahim F, Ullah H, Wadood A, Farooq RK, Shah SAA, et al.
    Sci Rep, 2020 06 30;10(1):10673.
    PMID: 32606439 DOI: 10.1038/s41598-020-67414-7
    In continuation of our work on enzyme inhibition, the benzofuran-based-thiazoldinone analogues (1-14) were synthesized, characterized by HREI-MS, 1H and 13CNMR and evaluated for urease inhibition. Compounds 1-14 exhibited a varying degree of urease inhibitory activity with IC50 values between 1.2 ± 0.01 to 23.50 ± 0.70 µM when compared with standard drug thiourea having IC50 value 21.40 ± 0.21 µM. Compound 1, 3, 5 and 8 showed significant inhibitory effects with IC50 values 1.2 ± 0.01, 2.20 ± 0.01, 1.40 ± 0.01 and 2.90 ± 0.01 µM respectively, better than the rest of the series. A structure activity relationship (SAR) of this series has been established based on electronic effects and position of different substituents present on phenyl ring. Molecular docking studies were performed to understand the binding interaction of the compounds.
    Matched MeSH terms: Benzofurans/chemical synthesis*; Benzofurans/pharmacology*
  5. Anti-inflammatory effects of mulberry (Morus alba L.) root bark and its active compounds
    Wu YX, Kim YJ, Kwon TH, Tan CP, Son KH, Kim T
    Nat Prod Res, 2020 Jun;34(12):1786-1790.
    PMID: 30470128 DOI: 10.1080/14786419.2018.1527832
    Mulberry (Morus alba L.) root bark (MRB) was extracted using methanol and the extracts were subjected to tests of anti-inflammatory effects. The ethyl acetate fraction demonstrated the best anti-inflammatory effects. Purified compounds, sanggenon B, albanol B and sanggenon D, showed inhibitory effects on NO production in LPS-stimulated RAW264.7 cells and albanol B demonstrated the best anti-inflammatory effects. Regarding the underlying molecular mechanisms, further investigations showed that treatments with Albanol B reduced production of pro-inflammatory cytokines and decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results would contribute to development of novel anti-inflammatory drugs from MRB.
    Matched MeSH terms: Benzofurans/isolation & purification
  6. Improved lovastatin production by inhibiting (+)-geodin biosynthesis in Aspergillus terreus
    Hasan H, Abd Rahim MH, Campbell L, Carter D, Abbas A, Montoya A
    N Biotechnol, 2019 Sep 25;52:19-24.
    PMID: 30995533 DOI: 10.1016/j.nbt.2019.04.003
    Lovastatin is widely prescribed to reduce elevated levels of cholesterol and prevent heart-related diseases. Cultivation of Aspergillus terreus (ATCC 20542) with carbohydrates or low-value feedstocks such as glycerol produces lovastatin as a secondary metabolite and (+)-geodin as a by-product. An A. terreus mutant strain was developed (gedCΔ) with a disrupted (+)-geodin biosynthesis pathway. The gedCΔ mutant was created by inserting the antibiotic marker hygromycin B (hyg) within the gedC gene that encodes emodin anthrone polyketide synthase (PKS), a primary gene responsible for initiating (+)-geodin biosynthesis. The effects of emodin anthrone PKS gene disruption on (+)-geodin and lovastatin biosynthesis and the production of the precursors acetyl-CoA and malonyl-CoA were investigated with cultures based on glycerol alone and in combination with lactose. The gedCΔ strain showed improved lovastatin production, particularly when cultivated on the glycerol-lactose mixture, increasing lovastatin production by 80% (113 mg/L) while simultaneously inhibiting (+)-geodin biosynthesis compared to the wild-type strain. This study thus shows that suppression of the (+)-geodin pathway increases lovastatin yield and demonstrates a practical approach of manipulating carbon flux by modulating enzyme activity.
    Matched MeSH terms: Benzofurans/metabolism*
  7. The investigation of media components for optimal metabolite production of Aspergillus terreus ATCC 20542
    Abd Rahim MH, Lim EJ, Hasan H, Abbas A
    J Microbiol Methods, 2019 09;164:105672.
    PMID: 31326443 DOI: 10.1016/j.mimet.2019.105672
    PURPOSE: This study aimed to assess the effect of nitrogen, salt and pre-culture conditions on the production of lovastatin in A. terreus ATCC 20542.

    METHODS: Different combinations of nitrogen sources, salts and pre-culture combinations were applied in the fermentation media and lovastatin yield was analysed chromatographically.

    RESULT: The exclusion of MnSO4 ·5H2O, CuSO4·5H2O and FeCl3·6H2O were shown to significantly improve lovastatin production (282%), while KH2PO4, MgSO4·7H2O, and NaCl and ZnSO4·7H2O were indispensable for good lovastatin production. Simple nitrogen source (ammonia) was unfavourable for morphology, growth and lovastatin production. In contrast, yeast extract (complex nitrogen source) produced the highest lovastatin yield (25.52 mg/L), while powdered soybean favoured the production of co-metabolites ((+)-geodin and sulochrin). Intermediate lactose: yeast extract (5:4) ratio produced the optimal lovastatin yield (12.33 mg/L) during pre-culture, while high (5:2) or low (5:6) lactose to yeast extract ratio produced significantly lower lovastatin yield (7.98 mg/L and 9.12 mg/L, respectively). High spore concentration, up to 107 spores/L was shown to be beneficial for lovastatin, but not for co-metabolite production, while higher spore age was shown to be beneficial for all of its metabolites.

    CONCLUSION: The findings from these investigations could be used for future cultivation of A. terreus in the production of desired metabolites.

    Matched MeSH terms: Benzofurans
  8. Fulltext Multi-targeting aurones with monoamine oxidase and amyloid-beta inhibitory activities: Structure-activity relationship and translating multi-potency to neuroprotection
    Liew KF, Lee EH, Chan KL, Lee CY
    Biomed Pharmacother, 2019 Feb;110:118-128.
    PMID: 30466001 DOI: 10.1016/j.biopha.2018.11.054
    Previously, a series of aurones bearing amine and carbamate functionalities was synthesized and evaluated for their cholinesterase inhibitory activity and drug-like attributes. In the present study, these aurones were evaluated for their multi-targeting properties in two Alzheimer's disease (AD)-related activities namely, monoamine oxidase (MAO) and amyloid-beta (Aβ) inhibition. Evaluation of the aurones for MAO inhibitory activity disclosed several potent selective inhibitors of MAO-B, particularly those with 6-methoxyl group attached at ring A. Of the different amine moieties attached as side chains, pyrrolidine-bearing aurones were prominent as represented by 2-2, the most potent inhibitor. Evaluation on the Aβ aggregation inhibition identified 4-3 as the best inhibitor with a percentage inhibition comparable to that of a known Aβ inhibitor curcumin. Examination on the neuroprotective ability of the more drug-like aurone 4-3 in two Caenorhabditis elegans neurodegeneration models showed 4-3 to protect the nematodes against both Aβ- and 6-hydroxydopamine-induced toxicities. These new activities further support 4-3 as a promising lead to develop the aurones as potential multipotent agents for neurodegenerative diseases.
    Matched MeSH terms: Benzofurans/administration & dosage*; Benzofurans/chemistry
  9. Fulltext The pharmacology and phytochemistry of Acalypha indica
    Wan Ya, W. N., Mohsin, H. F., Abdul Wahab, I.
    Malaysian Journal of Medicine and Health Sciences, 2019;15(102):55-55.
    MyJurnal
    Introduction: Acalypha indica is commonly referred to as “pokok kucing galak”. It is an herbaceous species that grow along the earth’s equator line, including the wet, temperate and tropical regions. Domestic cats experience the effect of this plant by reacting very favorably to the root. The first compilation of the ethnopharmacology and phytochemistry of the Acalypha plants was published. This genus is the fourth largest genus of the Euphorbiaceae family, with about 500 species. However, the review only represents about one third of the species from the Acalypha genus. Methods: Hence, this study is performed to obtain updates on the biochemistry of this plant, via literature search. Results: From the articles, almost every part of the plant, including the leaves, stems and roots, are used as traditional remedies. Local people consume the plant for therapeutic purposes such as anthelminthic, anti-ulcer, anti-bacteria, anti-microbial and wound healing. In homeopathy practice, it is used for asthma and bronchitis. Nevertheless,
    there is still a potential risk of using A. indica. It was reported that this traditional medicine could induce Intravascular haemolysis in patients with a glucose-6-phosphate-dehydrogenase (G6PD) deficiency. Clinical evaluations of Acalypha extract could be utilized to justify the ethnomedicinal claims and for the safety of its therapeutic applications. Meanwhile, there is an increase in the phytochemical and chromatographic experiments of A. indica that could introduce the extract’s role in pharmaceutical, nutraceutical, zoology and veterinary fields. It contains secondary metabolites, including dihydroactinidiolide; a terpenoid, alkaloids, flavonoids and steroids, for example, brassicasterol. Conclusion: The finding of this review concludes that Acalypha is a natural source, worth to be further investigated. It is hoped that new biologically active constituents could be discovered, since only few Acalypha species were comprehensively studied.
    Matched MeSH terms: Benzofurans
  10. Anticancer potential of rosmarinic acid and its improved production through biotechnological interventions and functional genomics
    Swamy MK, Sinniah UR, Ghasemzadeh A
    Appl Microbiol Biotechnol, 2018 Sep;102(18):7775-7793.
    PMID: 30022261 DOI: 10.1007/s00253-018-9223-y
    Rosmarinic acid (RA) is a highly valued natural phenolic compound that is very commonly found in plants of the families Lamiaceae and Boraginaceae, including Coleus blumei, Heliotropium foertherianum, Rosmarinus officinalis, Perilla frutescens, and Salvia officinalis. RA is also found in other members of higher plant families and in some fern and horned liverwort species. The biosynthesis of RA is catalyzed by the enzymes phenylalanine ammonia lyase and cytochrome P450-dependent hydroxylase using the amino acids tyrosine and phenylalanine. Chemically, RA can be produced via methods involving the esterification of 3,4-dihydroxyphenyllactic acid and caffeic acid. Some of the derivatives of RA include melitric acid, salvianolic acid, lithospermic acid, and yunnaneic acid. In plants, RA is known to have growth-promoting and defensive roles. Studies have elucidated the varied pharmacological potential of RA and its derived molecules, including anticancer, antiangiogenic, anti-inflammatory, antioxidant, and antimicrobial activities. The demand for RA is therefore, very high in the pharmaceutical industry, but this demand cannot be met by plants alone because RA content in plant organs is very low. Further, many plants that synthesize RA are under threat and near extinction owing to biodiversity loss caused by unscientific harvesting, over-collection, environmental changes, and other inherent features. Moreover, the chemical synthesis of RA is complicated and expensive. Alternative approaches using biotechnological methodologies could overcome these problems. This review provides the state of the art information on the chemistry, sources, and biosynthetic pathways of RA, as well as its anticancer properties against different cancer types. Biotechnological methods are also discussed for producing RA using plant cell, tissue, and organ cultures and hairy-root cultures using flasks and bioreactors. The recent developments and applications of the functional genomics approach and heterologous production of RA in microbes are also highlighted. This chapter will be of benefit to readers aiming to design studies on RA and its applicability as an anticancer agent.
    Matched MeSH terms: Benzofurans
  11. Fulltext Chalcomoracin is a potent anticancer agent acting through triggering Oxidative stress via a mitophagy- and paraptosis-dependent mechanism
    Han H, Chou CC, Li R, Liu J, Zhang L, Zhu W, et al.
    Sci Rep, 2018 06 22;8(1):9566.
    PMID: 29934599 DOI: 10.1038/s41598-018-27724-3
    Chalocomoracin (CMR), one of the major secondary metabolites found in fungus-infected mulberry leaves, is a potent anticancer agent. However, its anticancer mechanism remains elusive. Here, we demonstrated the potent anti-tumor activity and molecular mechanism of CMR both in vitro and in vivo. We showed for the first time that CMR treatment markedly promoted paraptosis along with extensive cytoplasmic vacuolation derived from the endoplasmic reticulum, rather than apoptosis, in PC-3 and MDA-MB-231cell lines. Additional studies revealed that ectopic expression of Myc-PINK1 (PTEN-induced kinase 1), a key regulator of mitophagy, rendered LNCap cells susceptible to CMR-induced paraptosis, suggesting that the mitophagy-dependent pathway plays a crucial role in inducing paraptosis by activating PINK1. CMR treatment directly upregulated PINK1 and downregulated Alix genes in MDA-MB-231 and PC-3 cell lines. Furthermore, mitophagy signaling and paraptosis with cytoplasmic vacuolation could be blocked by antioxidant N-acetylcysteine (NAC), indicating the novel pathway was triggered by reactive oxygen species (ROS) production. An in vivo MDA-MB-231 xenograft tumor model revealed that CMR suppressed tumor growth by inducing vacuolation production through the same signal changes as those observed in vitro. These data suggest that CMR is a potential therapeutic entity for cancer treatment through a non-apoptotic pathway.
    Matched MeSH terms: Benzofurans/pharmacology*
  12. Phytochemical profile of Orthosiphon aristatus extracts after storage: Rosmarinic acid and other caffeic acid derivatives
    Chua LS, Lau CH, Chew CY, Ismail NIM, Soontorngun N
    Phytomedicine, 2018 Jan 15;39:49-55.
    PMID: 29433683 DOI: 10.1016/j.phymed.2017.12.015
    BACKGROUND: Orthosiphon aristatus (Blume) Miq. is a medicinal herb which is traditionally used for the treatment of diabetes and kidney diseases in South East Asia. Previous studies reported higher concentration of antioxidative phytochemicals, especially rosmarinic acid (ester of caffeic acid) and other caffeic acid derivatives in this plant extract than the other herbs such as rosemary and sage which are usually used as raw materials to produce rosmarinic acid supplement in the market.

    PURPOSE: The phytochemical profile of O. aristatus was investigated at different storage durations for quality comparison.

    METHODS: The phytochemicals were extracted from the leaves and stems of O. aristatus using a reflux reactor. The extracts were examined for total phenolic and flavonoid contents, as well as their antioxidant capacities, in terms of radical scavenging, metal chelating and reducing power. The phytochemical profiles were also analyzed by unsupervised principal component analysis and hierarchical cluster analysis, in relation to the factor of storage at 4 °C for 5 weeks.

    RESULTS: The leaf extract was likely to have more phytochemicals than stem extract, particularly caffeic acid derivatives including glycosylated and alkylated caffeic acids. This explains higher ratio of total phenolic content to total flavonoid content with higher antioxidant capacities for the leaf extracts. Rosmarinic acid dimer and salvianolic acid B appeared to be the major constituents, possibly contributing to the previously reported pharmacological properties. However, the phytochemical profiles were found changing, even though the extracts were stored in the refrigerator (4 °C). The change was significantly observed at the fifth week based on the statistical pattern recognition technique.

    CONCLUSION: O. aristatus could be a promising source of rosmarinic acid and its dimer, as well as salvianolic acid B with remarkably antioxidant properties. The phytochemical profile was at least stable for a month stored at 4 °C. It is likely to be a good choice of herbal tea with comparable radical scavenging activity, but lower caffeine content than other tea samples.

    Matched MeSH terms: Benzofurans/analysis; Benzofurans/pharmacology
  13. Synthesis and in vitro study of benzofuran hydrazone derivatives as novel alpha-amylase inhibitor
    Taha M, Shah SAA, Imran S, Afifi M, Chigurupati S, Selvaraj M, et al.
    Bioorg Chem, 2017 12;75:78-85.
    PMID: 28918064 DOI: 10.1016/j.bioorg.2017.09.002
    The α-amylase acts as attractive target to treat type-2 diabetes mellitus. Therefore in discovering a small molecule as α-amylase inhibitor, we have synthesized benzofuran carbohydrazide analogs (1-25), characterized through different spectroscopic techniques such as 1HNMR and EI-MS. All screened analog shows good α-amylase inhibitory potentials with IC50 value ranging between 1.078±0.19 and 2.926±0.05µM when compared with acarbose having IC50=0.62±0.22µM. Only nine analogs among the series such as analogs 3, 5, 7, 8, 10, 12, 21, 23 and 24 exhibit good inhibitory potential with IC50 values 1.644±0.128, 1.078±0.19, 1.245±0.25, 1.843±0.19, 1.350±0.24, 1.629±0.015, 1.353±0.232, 1.359±0.119 and 1.488±0.07µM when compare with standard drug acarbose. All other analogs showed good to moderate α-amylase inhibitory potentials. The SAR study was conducted on the basis of substituent difference at the phenyl ring. The binding interaction between analogs and active site of enzyme was confirmed by docking studies.
    Matched MeSH terms: Benzofurans/chemistry*
  14. Treatment with salvianolic acid B restores endothelial function in angiotensin II-induced hypertensive mice
    Ling WC, Liu J, Lau CW, Murugan DD, Mustafa MR, Huang Y
    Biochem Pharmacol, 2017 Jul 15;136:76-85.
    PMID: 28396195 DOI: 10.1016/j.bcp.2017.04.007
    Salvianolic acid B (Sal B) is one of the most abundant phenolic acids derived from the root of Danshen with potent anti-oxidative properties. The present study examined the vasoprotective effect of Sal B in hypertensive mice induced by angiotensin II (Ang II). Sal B (25mg/kg/day) was administered via oral gavage for 11days to Ang II (1.2mg/kg/day)-infused C57BL/6J mice (8-10weeks old). The vascular reactivity (both endothelium-dependent relaxations and contractions) in mouse arteries was examined by wire myography. The production of reactive oxygen species (ROS), protein level and localization of angiotensin AT1 receptors and the proteins involved in ROS formation were evaluated using dihydroethidium (DHE) fluorescence, lucigenin-enhanced chemiluminescence, immunohistochemistry and Western blotting, respectively. The changes of ROS generating proteins were also assessed in vitro in human umbilical vein endothelial cells (HUVECs) exposed to Ang II with and without co-treatment with Sal B (0.1-10nM). Oral administration of Sal B reversed the Ang II-induced elevation of arterial systolic blood pressure in mice, augmented the impaired endothelium-dependent relaxations and attenuated the exaggerated endothelium-dependent contractions in both aortas and renal arteries of Ang II-infused mice. In addition, Sal B treatment normalized the elevated levels of AT1 receptors, NADPH oxidase subunits (NOx-2 and NOx-4) and nitrotyrosine in arteries of Ang II-infused mice or in Ang II-treated HUVECs. In summary, the present study provided additional evidence demonstrating that Sal B treatment for 11days reverses the impaired endothelial function and with a marked inhibition of AT1 receptor-dependent vascular oxidative stress. This vasoprotective and anti-oxidative action of Sal B most likely contributes to the anti-hypertensive action of the plant-derived compound.
    Matched MeSH terms: Benzofurans/pharmacology; Benzofurans/therapeutic use*
  15. Assessment of the Blood-Brain Barrier Permeability of Potential Neuroprotective Aurones in Parallel Artificial Membrane Permeability Assay and Porcine Brain Endothelial Cell Models
    Liew KF, Hanapi NA, Chan KL, Yusof SR, Lee CY
    J Pharm Sci, 2017 02;106(2):502-510.
    PMID: 27855959 DOI: 10.1016/j.xphs.2016.10.006
    Previously, several aurone derivatives were identified with promising neuroprotective activities. In developing these compounds to target the central nervous system (CNS), an assessment of their blood-brain barrier (BBB) permeability was performed using in vitro BBB models: parallel artificial membrane permeability assay-BBB which measures passive permeability and primary porcine brain endothelial cell model which enables determination of the involvement of active transport mechanism. Parallel artificial membrane permeability assay-BBB identified most compounds with high passive permeability, with 3 aurones having exceptional Pevalues highlighting the importance of basic amine moieties and optimal lipophilicity for good passive permeability. Bidirectional permeability assays with porcine brain endothelial cell showed a significant net influx permeation of the aurones indicating a facilitated uptake mechanism in contrast to donepezil, a CNS drug included in the evaluation which only displayed passive permeation. From pH-dependent permeability assay coupled with data analysis using pCEL-X software, intrinsic transcellular permeability (Po) of a representative aurone 4-3 was determined, considering factors such as the aqueous boundary layer that may hinder accurate in vitro to in vivo correlation. The Po value determined supported the in vivo feasibility of the aurone as a CNS-active compound.
    Matched MeSH terms: Benzofurans/pharmacokinetics*; Benzofurans/chemistry*
  16. Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles
    Taha M, Ismail NH, Imran S, Wadood A, Rahim F, Saad SM, et al.
    Bioorg Chem, 2016 Jun;66:117-23.
    PMID: 27149363 DOI: 10.1016/j.bioorg.2016.04.006
    Twenty derivatives of 5-aryl-2-(6'-nitrobenzofuran-2'-yl)-1,3,4-oxadiazoles (1-20) were synthesized and evaluated for their α-glucosidase inhibitory activities. Compounds containing hydroxyl and halogens (1-6, and 8-18) were found to be five to seventy folds more active with IC50 values in the range of 12.75±0.10-162.05±1.65μM, in comparison with the standard drug, acarbose (IC50=856.45±5.60μM). Current study explores the α-glucosidase inhibition of a hybrid class of compounds of oxadiazole and benzofurans. These findings may invite researchers to work in the area of treatment of hyperglycemia. Docking studies showed that most compounds are interacting with important amino acids Glu 276, Asp 214 and Phe 177 through hydrogen bonds and arene-arene interaction.
    Matched MeSH terms: Benzofurans/chemical synthesis; Benzofurans/pharmacology*; Benzofurans/chemistry
  17. Cyclopenta[b]benzofuran and Secodammarane Derivatives from the Stems of Aglaia stellatopilosa
    Othman N, Pan L, Mejin M, Voong JC, Chai HB, Pannell CM, et al.
    J Nat Prod, 2016 Apr 22;79(4):784-91.
    PMID: 26974604 DOI: 10.1021/acs.jnatprod.5b00810
    Four new 2,3-secodammarane triterpenoids, stellatonins A-D (3-6), together with a new 3,4-secodammarane triterpenoid, stellatonin E (7), and the known silvestrol (1), 5‴-episilvestrol (2), and β-sitosterol, were isolated from a methanol extract of the stems of Aglaia stellatopilosa through bioassay-guided fractionation. The structures of the new compounds were elucidated using spectroscopic and chemical methods. The compounds were evaluated for their cytotoxic activity against three human cancer cell lines and for their antimicrobial activity using a microtiter plate assay against a panel of Gram-positive and Gram-negative bacteria and fungi.
    Matched MeSH terms: Benzofurans/isolation & purification*; Benzofurans/chemistry
  18. Fulltext Benzofuranyl Esters: Synthesis, Crystal Structure Determination, Antimicrobial and Antioxidant Activities
    Kumar CS, Then LY, Chia TS, Chandraju S, Win YF, Sulaiman SF, et al.
    Molecules, 2015 Sep 11;20(9):16566-81.
    PMID: 26378514 DOI: 10.3390/molecules200916566
    A series of five new 2-(1-benzofuran-2-yl)-2-oxoethyl 4-(un/substituted)benzoates 4(a-e), with the general formula of C₈H₅O(C=O)CH₂O(C=O)C₆H₄X, X = H, Cl, CH₃, OCH₃ or NO₂, was synthesized in high purity and good yield under mild conditions. The synthesized products 4(a-e) were characterized by FTIR, ¹H-, (13)C- and ¹H-(13)C HMQC NMR spectroscopic analysis and their 3D structures were confirmed by single-crystal X-ray diffraction studies. These compounds were screened for their antimicrobial and antioxidant activities. The tested compounds showed antimicrobial ability in the order of 4b < 4a < 4c < 4d < 4e and the highest potency with minimum inhibition concentration (MIC) value of 125 µg/mL was observed for 4e. The results of antioxidant activities revealed the highest activity for compound 4e (32.62% ± 1.34%) in diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, 4d (31.01% ± 4.35%) in ferric reducing antioxidant power (FRAP) assay and 4a (27.11% ± 1.06%) in metal chelating (MC) activity.
    Matched MeSH terms: Benzofurans/chemistry*
  19. Molecular docking and dynamic simulation evaluation of Rohinitib - Cantharidin based novel HSF1 inhibitors for cancer therapy
    Agarwal T, Annamalai N, Khursheed A, Maiti TK, Arsad HB, Siddiqui MH
    J Mol Graph Model, 2015 Sep;61:141-9.
    PMID: 26245696 DOI: 10.1016/j.jmgm.2015.07.003
    Recent developments in the target based cancer therapies have identified HSF1 as a novel non oncogenic drug target. The present study delineates the design and molecular docking evaluation of Rohinitib (RHT) - Cantharidin (CLA) based novel HSF1 inhibitors for target-based cancer therapy. Here, we exploited the pharmacophoric features of both the parent ligands for the design of novel hybrid HSF1 inhibitors. The RHT-CLA ligands were designed and characterized for ADME/Tox features, interaction with HSF1 DNA binding domain and their pharmacophoric features essential for interaction. From the results, amino acid residues Ala17, Phe61, His63, Asn65, Ser68, Arg71 and Gln72 were found crucial for HSF1 interaction with the Heat shock elements (HSE). The hybrid ligands had better affinity towards the HSF1 DNA binding domain, in comparison to RHT or CLA and interacted with most of the active site residues. Additionally, the HSF1-ligand complex had a reduced affinity towards HSE in comparison to native HSF1. Based on the results, ligand RC15 and RC17 were non carcinogenic, non mutagenic, completely biodegradable under aerobic conditions, had better affinity for HSF1 (1.132 and 1.129 folds increase respectively) and diminished the interaction of HSF1 with HSE (1.203 and 1.239 folds decrease respectively). The simulation analysis also suggested that the ligands formed a stable complex with HSF1, restraining the movement of active site residues. In conclusion, RHT-CLA hybrid ligands can be used as a potential inhibitor of HSF1 for non-oncogene target based cancer therapy.
    Matched MeSH terms: Benzofurans/chemistry*
  20. Blood-brain barrier permeable anticholinesterase aurones: synthesis, structure-activity relationship, and drug-like properties
    Liew KF, Chan KL, Lee CY
    Eur J Med Chem, 2015 Apr 13;94:195-210.
    PMID: 25768702 DOI: 10.1016/j.ejmech.2015.02.055
    A series of novel aurones bearing amine and carbamate functionalities at various positions (rings A and/or B) of the scaffold was synthesized and evaluated for their acetylcholinesterase and butyrylcholinesterase inhibitory activities. Structure-activity relationship study disclosed several potent submicromolar acetylcholinesterase inhibitors (AChEIs) particularly aurones bearing piperidine and pyrrolidine moieties at ring A or ring B. Bulky groups particularly methoxyls, and carbamate to a lesser extent, at either rings were also prominently featured in these AChEI aurones as exemplified by the trimethoxyaurone 4-3. The active aurones exhibited a lower butyrylcholinesterase inhibition. A 3'-chloroaurone 6-3 originally designed to improve the metabolic stability of the scaffold was the most potent of the series. Molecular docking simulations showed these AChEI aurones to adopt favourable binding modes within the active site gorge of the Torpedo californica AChE (TcAChE) including an unusual chlorine-π interaction by the chlorine of 6-3 to establish additional bondings to hydrophobic residues of TcAChE. Evaluation of the potent aurones for their blood-brain barrier (BBB) permeability and metabolic stability using PAMPA-BBB assay and in vitro rat liver microsomes (RLM) identified 4-3 as an aurone with an optimal combination of high passive BBB permeability and moderate CYP450 metabolic stability. LC-MS identification of a mono-hydroxylated metabolite found in the RLM incubation of 4-3 provided an impetus for further improvement of the compound. Thus, 4-3, discovered within this present series is a promising, drug-like lead for the development of the aurones as potential multipotent agents for Alzheimer's disease.
    Matched MeSH terms: Benzofurans/chemistry
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