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  1. Hematpoor A, Liew SY, Azirun MS, Awang K
    Sci Rep, 2017 10 03;7(1):12576.
    PMID: 28974710 DOI: 10.1038/s41598-017-12898-z
    Hexane, dichloromethane and methanol extracts of the roots of Piper sarmentosum Roxb. were screened for toxicity towards Sitophilus oryzae (L.), Rhyzopertha dominica (F.), and Plodia interpunctella (Hübner) and the hexane extract exhibited the highest mortality percentage. Bioassay-guided fractionation of the hexane extract resulted in the isolation of asaricin 1, isoasarone 2, and trans-asarone 3. Asaricin 1 and isoasarone 2 were the most toxic compounds to Sitophilus oryzae, Rhyzopertha dominica, and Plodia interpunctella. Sitophilus oryzae and Rhyzopertha dominica exposed to asaricin 1 and isoasarone 2 required the lowest median lethal time. Insecticidal activity of trans-asarone 3 showed consistent toxicity throughout the 60 days towards all three insects as compared to asaricin 1 and isoasarone 2. Asaricin 1 and isoasarone 2 at different doses significantly reduced oviposition and adult emergence of the three insects in treated rice. Trans-asarone 3 had lowest toxicity with highest LC and LT values in all tested insects relative to its mild oviposition inhibition and progeny activity. Moreover, asaricin 1 and isoasarone 2 significantly inhibited acetylcholinesterase in comparison with trans-asarone 3 and the control. Acetylcholinesterase inhibition of Rhyzopertha dominica and Plodia interpunctella by asaricin 1 and isoasarone 2 were lower than that of Sitophilus oryzae, which correlated with their higher resistance.
  2. Fathima A, Ilankoon IMSK, Zhang Y, Chong MN
    Sci Total Environ, 2024 Feb 20;912:169186.
    PMID: 38086487 DOI: 10.1016/j.scitotenv.2023.169186
    Impetus to minimise the energy and carbon footprints of evolving wastewater resource recovery facilities has promoted the development of microbial electrochemical systems (MES) as an emerging energy-neutral and sustainable platform technology. Using separators in dual-chamber MES to isolate anodic and cathodic environments creates endless opportunities for its myriad applications. Nevertheless, the high internal resistance and the complex interdependencies among various system factors have challenged its scale-up. This critical review employed a systems approach to examine the complex interdependencies and practical issues surrounding the implementation and scalability of dual-chamber MES, where the anodic and cathodic reactions are mutually appraised to improve the overall system efficiency. The robustness and stability of anodic biofilms in large-volume MES is dependent on its inoculum source, antecedent history and enrichment strategies. The composition and anode-respiring activity of these biofilms are modulated by the anolyte composition, while their performance demands a delicate balance between the electrode size, macrostructure and the availability of substrates, buffers and nutrients when using real wastewater as anolyte. Additionally, the catholyte governed the reduction environment and associated energy consumption of MES with scalable electrocatalysts needed to enhance the sluggish reaction kinetics for energy-efficient resource recovery. A comprehensive assessment of the dual-chamber reactor configuration revealed that the tubular, spiral-wound, or plug-in modular MES configurations are suitable for pilot-scale, where it could be designed more effectively using efficient electrode macrostructure, suitable membranes and bespoke strategies for continuous operation to maximise their performance. It is anticipated that the critical and analytical understanding gained through this review will support the continuous development and scaling-up of dual-chamber MES for prospective energy-neutral treatment of wastewater and simultaneous circular management of highly relevant environmental resources.
  3. Fathima A, Ilankoon IMSK, Chong MN
    Chemosphere, 2024 Sep;363:142800.
    PMID: 38977249 DOI: 10.1016/j.chemosphere.2024.142800
    Microbial fuel cells (MFC) are emerging energy-efficient systems for copper (Cu) electrowinning from waste streams by coupling it with anodic oxidation of organics in wastewater. However, there is a lack of research examining scalable electrocatalysts for Cu electrowinning at low cathodic overpotentials in highly saline catholytes often found in e-waste leachates. The challenge of developing resilient anodic biofilms that withstand the antagonistic effects of ions migrating from catholytes in saline MFC also needs to be addressed. In this study, polypyrrole (PPy) cathodic electrocatalysts were developed and coupled with a robust halophilic anodic biofilm in MFC to improve the kinetics of Cu electrowinning from acidic chloride-based catholytes. Electrochemical characterisation of these cathodes revealed shuttling of electrons by redox-active PPy via the formation of intermediate Cu+-complexes as an energy-efficient pathway for producing metallic Cu. High power densities ranging from 0.63 ± 0.17 to 0.73 ± 0.05 W m-2 were achieved with undoped-PPy and phytic acid doped-PPy cathodes with simultaneous recovery of ∼97% Cu. These electrocatalysts also exhibited low charge transfer resistance (3-8 mΩ m2) that met the requisites for scalable cathodes in MFC. However, a decrease in the efficiency of PPy cathodes was observed over 5 d due to competing reactions at their interfaces, including re-oxidation of deposited Cu and cathodic corrosion, with further studies suggested to enhance their corrosion resistance. Nonetheless, integrating PPy electrocatalysts for Cu electrowinning in saline MFC has advanced its outlooks as an energy-efficient downstream process for urban mining of Cu from e-waste.
  4. Hematpoor A, Liew SY, Chong WL, Azirun MS, Lee VS, Awang K
    PLoS One, 2016;11(5):e0155265.
    PMID: 27152416 DOI: 10.1371/journal.pone.0155265
    Aedes aegypti, Aedes albopictus and Culex quinquefasciatus are vectors of dengue fever and West Nile virus diseases. This study was conducted to determine the toxicity, mechanism of action and the binding interaction of three active phenylpropanoids from Piper sarmentosum (Piperaceae) toward late 3rd or early 4th larvae of above vectors. A bioassay guided-fractionation on the hexane extract from the roots of Piper sarmentosum led to the isolation and identification of three active phenylpropanoids; asaricin 1, isoasarone 2 and trans-asarone 3. The current study involved evaluation of the toxicity and acetylcholinesterase (AChE) inhibition of these compounds against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae. Asaricin 1 and isoasarone 2 were highly potent against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus larvae causing up to 100% mortality at ≤ 15 μg/mL concentration. The ovicidal activity of asaricin 1, isoasarone 2 and trans-asarone 3 were evaluated through egg hatching. Asaricin 1 and isoasarone 2 showed potent ovicidal activity. Ovicidal activity for both compounds was up to 95% at 25μg/mL. Asaricin 1 and isoasarone 2 showed strong inhibition on acetylcholinesterase with relative IC50 values of 0.73 to 1.87 μg/mL respectively. These findings coupled with the high AChE inhibition may suggest that asaricin 1 and isoasarone 2 are neuron toxic compounds toward Aedes aegypti, Aedes albopictus and Culex quinquefasciatus. Further computational docking with Autodock Vina elaborates the possible interaction of asaricin 1 and isoasarone 2 with three possible binding sites of AChE which includes catalytic triads (CAS: S238, E367, H480), the peripheral sites (PAS: E72, W271) and anionic binding site (W83). The binding affinity of asaricin 1 and isoasarone 2 were relatively strong with asaricin 1 showed a higher binding affinity in the anionic pocket.
  5. Hematpoor A, Paydar M, Liew SY, Sivasothy Y, Mohebali N, Looi CY, et al.
    Chem Biol Interact, 2018 Jan 05;279:210-218.
    PMID: 29174417 DOI: 10.1016/j.cbi.2017.11.014
    The aim of the present study is to isolate bioactive compounds from the roots of Piper sarmentosum and examine the mechanism of action using human breast cancer cell line (MDA-MB-231). Bioassay guided-fractionation of methanolic extract led to the isolation of asaricin (1) and isoasarone (2). Asaricin (1) and isoasarone (2) had significant cytotoxicity towards MDA-MB-231. MCF-10A (human normal breast epithelial cells) cells are less sensitive than MDA-MB-231, but they respond to the treatment with the same unit of measurement. Both compounds increase reactive oxygen species (ROS), decrease mitochondrial membrane potential (MMP) and enhance cytochrome c release in treated MDA-MB-231 cells. Isoasarone (2) markedly elevated caspase -8 and -3/7 activities and caused a decline in nuclear NF-κB translocation, suggesting extrinsic, death receptor-linked apoptosis pathway. Quantitative PCR results of MDA-MB-231 treated with asaricin (1) and isoasarone (2) showed altered expression of Bcl-2: Bax level. The inhibitory potency of these isolates may support the therapeutic uses of these compounds in breast cancer.
  6. Nagaraja S, Ahmed SS, D R B, Goudanavar P, M RK, Fattepur S, et al.
    Molecules, 2022 Jul 06;27(14).
    PMID: 35889209 DOI: 10.3390/molecules27144336
    Diabetes mellitus (DM) and its complications are a severe public health concern due to the high incidence, morbidity, and mortality rates. The present study aims to synthesize and characterize silver nanoparticles (AgNPs) using the aqueous leaf extract of Psidium guajava (PGE) for investigating its antidiabetic activity. Psidium guajava silver nanoparticles (PGAg NPs) were prepared and characterized by various parameters. The in vivo study was conducted using PGE and PGAg NPs in Streptozotocin (STZ)-induced diabetic rats to assess their antidiabetic properties. STZ of 55 mg/kg was injected to induce diabetes. The PGE, PGAg NPs at a dose of 200 and 400 mg/kg and standard drug Metformin (100 mg/kg) were administered daily to diabetic rats for 21 days through the oral route. Blood glucose level, body weight changes, lipid profiles, and histopathology of the rats' liver and pancreas were examined. In the diabetic rats, PGE and PGAg NPs produced a drastic decrease in the blood glucose level, preventing subsequent weight loss and ameliorating lipid profile parameters. The histopathological findings revealed the improvements in pancreas and liver cells due to the repercussion of PGE and PGAg NPs. A compelling effect was observed in all doses of PGE and PGAg NPs; however, PGAg NPs exhibited a more promising result. Thus, from the results, it is concluded that the synthesized PGAg NPs has potent antidiabetic activity due to its enhanced surface area and smaller particle size of nanoparticles.
  7. Bano B, Arshia, Khan KM, Kanwal, Fatima B, Taha M, et al.
    Eur J Med Chem, 2017 Oct 20;139:849-864.
    PMID: 28865280 DOI: 10.1016/j.ejmech.2017.08.052
    In this study synthesis and β-glucuronidase inhibitory potential of 3/5/8 sulfonamide and 8-sulfonate derivatives of quinoline (1-40) are discussed. Studies reveal that all the synthetic compounds were found to have good inhibitory activity against β-glucuronidase. Nonetheless, compounds 1, 2, 5, 13, and 22-24 having IC50 values in the range of 1.60-8.40 μM showed superior activity than the standard saccharic acid 1,4-lactone (IC50 = 48.4 ± 1.25 μM). Moreover, molecular docking studies of selected compounds were also performed to see interactions between active compounds and binding sites. Structures of all the synthetic compounds were confirmed through (1)H NMR, EI-MS and HREI-MS spectroscopic techniques.
  8. Rafique R, Khan KM, Arshia, Kanwal, Chigurupati S, Wadood A, et al.
    Bioorg Chem, 2020 01;94:103195.
    PMID: 31451297 DOI: 10.1016/j.bioorg.2019.103195
    The current study describes the discovery of novel inhibitors of α-glucosidase and α-amylase enzymes. For that purpose, new hybrid analogs of N-hydrazinecarbothioamide substituted indazoles 4-18 were synthesized and fully characterized by EI-MS, FAB-MS, HRFAB-MS, 1H-, and 13C NMR spectroscopic techniques. Stereochemistry of the imine double bond was established by NOESY measurements. All derivatives 4-18 with their intermediates 1-3, were evaluated for in vitro α-glucosidase and α-amylase enzyme inhibition. It is worth mentioning that all synthetic compounds showed good inhibition potential in the range of 1.54 ± 0.02-4.89 ± 0.02 µM for α-glucosidase and for α-amylase 1.42 ± 0.04-4.5 ± 0.18 µM in comparison with the standard acarbose (IC50 value of 1.36 ± 0.01 µM). In silico studies were carried out to rationalize the mode of binding interaction of ligands with the active site of enzymes. Moreover, enzyme inhibitory kinetic characterization was also performed to understand the mechanism of enzyme inhibition.
  9. Rafique R, Khan KM, Arshia, Chigurupati S, Wadood A, Rehman AU, et al.
    Bioorg Chem, 2020 01;94:103410.
    PMID: 31732193 DOI: 10.1016/j.bioorg.2019.103410
    Over-expression of α-amylase enzyme causes hyperglycemia which lead to many physiological complications including oxidative stress, one of the most commonly associated problem with diabetes mellitus. Marketed α-amylase inhibitors such as acarbose, voglibose, and miglitol used to treat type-II diabetes mellitus, but also linked to several harmful effects. Therefore, it is essential to explore new and nontoxic antidiabetic agents with additional antioxidant properties. In this connection, a series of new N-sulfonohydrazide substituted indazoles 1-19 were synthesized by multistep reaction scheme and assessed for in vitro α-amylase inhibitory and radical (DPPH and ABTS) scavenging properties. All compounds were fully characterized by different spectroscopic techniques including 1H, 13C NMR, EI-MS, HREI-MS, ESI-MS, and HRESI-MS. Compounds showed promising α-amylase inhibitory activities (IC50 = 1.23 ± 0.06-4.5 ± 0.03 µM) as compared to the standard acarbose (IC50 1.20 ± 0.09 µM). In addition to that all derivatives were found good to moderate scavengers of DPPH (IC50 2.01 ± 0.13-5.3 ± 0.11) and ABTS (IC50 = 2.34 ± 0.07-5.5 ± 0.07 µM) radicals, in comparison with standard ascorbic acid having scavenging activities with IC50 = 1.99 ± 0.09 µM, and IC50 2.03 ± 0.11 µM for DPPH and ABTS radicals. In silico molecular docking study was conducted to rationalize the binding interaction of α-amylase enzyme with ligands. Compounds were observed as mixed type inhibitors in enzyme kinetic characterization.
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