Browsing by Author "Chonnikan Hanpaibool"

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    (-)-Kusunokinin as a Potential Aldose Reductase Inhibitor: Equivalency Observed via AKR1B1 Dynamics Simulation
    (2021-01-12) Tanotnon Tanawattanasuntorn; Tienthong Thongpanchang; Thanyada Rungrotmongkol; Chonnikan Hanpaibool; Potchanapond Graidist; Varomyalin Tipmanee; Chulalongkorn University; Mahidol University; Prince of Songkla University
    (-)-Kusunokinin performed its anticancer potency through CFS1R and AKT pathways. Its ambiguous binding target has, however, hindered the next development phase. Our study thus applied molecular docking and molecular dynamics simulation to predict the protein target from the pathways. Among various candidates, aldo-keto reductase family 1 member B1 (AKR1B1) was finally identified as a (-)-kusunokinin receptor. The predicted binding affinity of (-)-kusunokinin was better than the selected aldose reductase inhibitors (ARIs) and substrates. The compound also had no significant effect on AKR1B1 conformation. An intriguing AKR1B1 efficacy, with respect to the known inhibitors (epalrestat, zenarestat, and minalrestat) and substrates (UVI2008 and prostaglandin H2), as well as a similar interactive insight of the enzyme pocket, pinpointed an ARI equivalence of (-)-kusunokinin. An aromatic ring and a γ-butyrolactone ring shared a role with structural counterparts in known inhibitors. The modeling explained that the aromatic constituent contributed to π-πattraction with Trp111. In addition, the γ-butyrolactone ring bound the catalytic His110 using hydrogen bonds, which could lead to enzymatic inhibition as a consequence of substrate competitiveness. Our computer-based findings suggested that the potential of (-)-kusunokinin could be furthered by in vitro and/or in vivo experiments to consolidate (-)-kusunokinin as a new AKR1B1 antagonist in the future.
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    Resistance to the "last resort" antibiotic colistin: A single-zinc mechanism for phosphointermediate formation in MCR enzymes
    (2020-06-25) Emily Lythell; Reynier Suardíaz; Philip Hinchliffe; Chonnikan Hanpaibool; Surawit Visitsatthawong; A. Sofia F. Oliveira; A. Sofia F. Oliveira; Eric J.M. Lang; Panida Surawatanawong; Vannajan Sanghiran Lee; Thanyada Rungrotmongkol; Natalie Fey; James Spencer; Adrian J. Mulholland; University of Malaya; Chulalongkorn University; Universidad Complutense de Madrid; University of Portsmouth; University of Bristol; Mahidol University
    © 2020 The Royal Society of Chemistry. MCR (mobile colistin resistance) enzymes catalyse phosphoethanolamine (PEA) addition to bacterial lipid A, threatening the "last-resort"antibiotic colistin. Molecular dynamics and density functional theory simulations indicate that monozinc MCR supports PEA transfer to the Thr285 acceptor, positioning MCR as a mono-rather than multinuclear member of the alkaline phosphatase superfamily.
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    Theoretical analysis of orientations and tautomerization of genistein in β-cyclodextrin
    (2018-09-01) Chonnikan Hanpaibool; Tipsuda Chakcharoensap; Arifin; Yuh Hijikata; Stephan Irle; Peter Wolschann; Nawee Kungwan; Piamsook Pongsawasdi; Puey Ounjai; Thanyada Rungrotmongkol; Chulalongkorn University; Universitat Wien; Thailand Ministry of Education; Mahidol University; Chiang Mai University; Nagoya University
    © 2018 Genistein is an isoflavone with promising pharmaceutical applications. However, its low water solubility interferes with its potency, and therefore cyclodextrins (CDs) have been considered as possible drug delivery system (DDS). To investigate the complexation mechanism of genistein in cyclodextrin, we employed molecular dynamics (MD) simulations based on classical potentials and the density-functional tight-binding (DFTB) quantum chemical potential. Both classical and quantum chemical MD simulations predict that the phenol ring of genistein is preferentially complexed in the cavity of CD. The complexation process reduces the water-accessible solvation shell, and it is found that a hydrogen bond is formed between genistein and CD. The DFTB-based MD simulations reveal that spontaneous keto-enol tautomerization occurs even within a hundred picoseconds, which suggests that the encapsulated genistein is complexed in the ordinary enol form of the drug molecule. Analyses of the molecular charge distributions suggest that electrostatic interactions partially induce the complex formation, rather than extensive formation of hydrogen bonds.