Displaying publications 21 - 27 of 27 in total

Abstract:
Sort:
  1. Kandasamy M, Mak KK, Devadoss T, Thanikachalam PV, Sakirolla R, Choudhury H, et al.
    BMC Chem, 2019 Dec;13(1):117.
    PMID: 31572984 DOI: 10.1186/s13065-019-0633-4
    Background: The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N'-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature.

    Methods: NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using 'Keap1:Nrf2 Inhibitor Screening Assay Kit'. To obtain the insights on NQC's activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes.

    Results: NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human.

    Conclusion: NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

  2. Mohd Jusoh NH, Subki A, Yeap SK, Yap KC, Jaganath IB
    BMC Chem, 2019 Dec;13(1):134.
    PMID: 31891160 DOI: 10.1186/s13065-019-0653-0
    Background: Safety, environmental and economic setbacks are driving industries to find greener approaches to extract bioactive compounds from natural resources. Pressurized hot water extraction (PHWE) is among the solvent free and efficient methods for extracting bioactive compounds.

    Experimental: In this study, the suitability of PHWE for extracting bioactive compounds such as phenolics, hydrolysable tannins and flavonoids from Phyllanthus tenellus was investigated by UPLC-qTOF-MS.

    Results: Solvent properties of water are significantly increased through imposing temperature at 121 °C and pressure at 15 p.s.i. Pressurized hot water extraction obtained 991-folds higher hydrolysable tannins than methanol extraction.

    Conclusion: The extraction yields of hydrolysable tannins with PHWE was almost double of absolute methanol extraction.

  3. Lasekan O, Teoh LS
    BMC Chem, 2019 Dec;13(1):133.
    PMID: 31891159 DOI: 10.1186/s13065-019-0650-3
    Background: The aroma chemistry and the contribution of the aroma compounds to the anti-oxidative properties of roasted yam have yet to be characterized. The growing popularity of roasted yam in regions where they are being consumed calls for a concerted effort to elucidate their aroma chemistry as well as their anti-oxidative properties.

    Results: The aroma compounds in roasted white yam (Dioscorea rotundata) were isolated and identified using static headspace-gas chromatography-mass spectrometry (SH-GC-MS) and gas chromatography-olfactometry (GC-O). In addition, the anti-oxidative activities of the most abundant volatile heterocyclic compounds (2 pyrroles, 4 furans and 3 pyrazines) were evaluated on their inhibitory effect towards the oxidation of hexanal for a period of 30 days. Twenty-nine aroma-active compounds with a flavour dilution (FD) factor range of 2-256 and an array of odour notes were obtained. Among them, the highest odour activities (FD ≥ 128) factors were determined for 2-acetyl furan and 2-acetylpyrrole. Other compounds with significant FD factors ≥ 32 were; 2-methylpyrazine, ethyl furfural, and 5-hydroxy methyl furfural.

    Conclusion: Results of the anti-oxidative activity showed that the pyrroles exhibited the greatest antioxidant activity among all the tested heterocyclic compounds. This was followed by the furans and the pyrazines which had the least antioxidant activity.

  4. Kumar S, Sharma D, Narasimhan B, Ramasamy K, Shah SAA, Lim SM, et al.
    BMC Chem, 2019 Dec;13(1):96.
    PMID: 31355369 DOI: 10.1186/s13065-019-0613-8
    Heterocyclic 1,3-diazine nucleus is a valuable pharmacophore in the field of medicinal chemistry and exhibit a wide spectrum of biological activities. PharmMapper, a robust online tool used for establishing the target proteins based on reverse pharmacophore mapping. PharmMapper study is carried out to explore the pharmacological activity of 1,3-diazine derivatives using reverse docking program. PharmMapper, an open web server was used to recognize for all the feasible target proteins for the developed compounds through reverse pharmacophore mapping. The results were analyzed via molecular docking with maestro v11.5 (Schrodinger 2018-1) using GTPase HRas as possible target. The molecular docking studies displayed the binding behavior of 1,3-diazine within GTP binding pocket. From the docking study compounds s3 and s14 showed better docked score with anticancer potency against cancer cell line (HCT116). Hence, the GTPase HRas may be the possible target of 1,3-diazine derivatives for their anticancer activity where the retrieved information may be quite useful for developing rational drug designing. Furthermore the selected 1,3-diazine compounds were evaluated for their in vitro anticancer activity against murine macrophages cell line. 1,3-Diazine compounds exhibited good selectivity of the compounds towards the human colorectal carcinoma cell line instead of the murine macrophages. The toxicity study of the most active compounds was also performed on non cancerous HEK-293 cell line.
  5. Kumar S, Kaushik A, Narasimhan B, Shah SAA, Lim SM, Ramasamy K, et al.
    BMC Chem, 2019 Dec;13(1):85.
    PMID: 31384832 DOI: 10.1186/s13065-019-0601-z
    Pyrimidine nucleus is a significant pharmacophore that exhibited excellent pharmacological activities. A series of pyrimidine scaffolds was synthesized and its chemical structures were confirmed by physicochemical and spectral analysis. The synthesized compounds were evaluated for their antimicrobial potential towards Gram positive and negative bacteria as well as fungal species. They were also assessed for their anticancer activity toward a human colorectal carcinoma cell line (HCT116). Whilst results of antimicrobial potential revealed that compounds Ax2, Ax3, Ax8 and Ax14 exhibited better activity against tested microorganisms, the results of antiproliferative activity indicated that compounds Ax7 and Ax10 showed excellent activity against HCT116. Further, the molecular docking of pyrimidine derivatives Ax1, Ax9 and Ax10 with CDK8 (PDB id: 5FGK) protein indicated that moderate to better docking results within the binding pocket. Compounds Ax8 and Ax10 having significant antimicrobial and anticancer activities may be selected as lead compounds for the development of novel antimicrobial and anticancer agent, respectively.
  6. Tahlan S, Kumar S, Ramasamy K, Lim SM, Shah SAA, Mani V, et al.
    BMC Chem, 2019 Dec;13(1):90.
    PMID: 31384837 DOI: 10.1186/s13065-019-0608-5
    Benzimidazole is a valuable pharmacophore in the field of medicinal chemistry and exhibit wide spectrum of biological activity. Molecular docking technique is routinely used in modern drug discovery for understanding the drug-receptor interaction. The selected data set of synthesized benzimidazole compounds was evaluated for its in vitro anticancer activity against cancer cell lines (HCT116 and MCF7) by sulforhodamine B (SRB) assay. Further, molecular docking study of data set was carried out by Schrodinger-Maestro v11.5 using CDK-8 (PDB code: 5FGK) and ER-alpha (PDB code: 3ERT) as possible target for anticancer activity. Molecular docking results demonstrated that compounds 12, 16, N9, W20 and Z24 displayed good docking score with better interaction within crucial amino acids and corelate to their anticancer results. ADME results indicated that compounds 16, N9 and W20 have significant results within the close agreement of the Lipinski's rule of five and Qikprop rule within the range and these compounds may be taken as lead molecules for the discovery of new anticancer agents.
  7. Mehta S, Kumar S, Marwaha RK, Narasimhan B, Ramasamy K, Lim SM, et al.
    BMC Chem, 2019 Dec;13(1):113.
    PMID: 31517312 DOI: 10.1186/s13065-019-0629-0
    In the present study, a series of 2-(4-(2-chloroacetyl)piperazin-1-yl)-N-(2-(4-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)acetamide derivatives was synthesized and its chemical structures were confirmed by physicochemical and spectral characteristics. The synthesized compounds were evaluated for their in vitro antimicrobial (tube dilution technique) and anticancer (MTT assay) activities along with molecular docking study by Schrodinger 2018-1, maestro v11.5. The antimicrobial results indicated that compounds 3, 8, 11 and 12 displayed the significant antimicrobial activity and comparable to the standards drugs (ciprofloxacin and fluconazole). The anticancer activity results indicated that compound 5 have good anticancer activity among the synthesized compounds but lower active than the standard drugs (5-fluorouracil and tomudex). Molecular docking study demonstrated that compounds 5 and 7 displayed the good docking score with better anticancer potency within the binding pocket and these compounds may be used as a lead for rational drug designing for the anticancer molecules.
Related Terms
Filters
Contact Us

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links