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    Item type:Publication,
    Towards reproducible computational drug discovery
    (2020-01-28)
    Schaduangrat, Nalini
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    Lampa, Samuel
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    Simeon, Saw
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    Gleeson, Matthew Paul
    ;
    Spjuth, Ola
    The reproducibility of experiments has been a long standing impediment for further scientific progress. Computational methods have been instrumental in drug discovery efforts owing to its multifaceted utilization for data collection, pre-processing, analysis and inference. This article provides an in-depth coverage on the reproducibility of computational drug discovery. This review explores the following topics: (1) the current state-of-the-art on reproducible research, (2) research documentation (e.g. electronic laboratory notebook, Jupyter notebook, etc.), (3) science of reproducible research (i.e. comparison and contrast with related concepts as replicability, reusability and reliability), (4) model development in computational drug discovery, (5) computational issues on model development and deployment, (6) use case scenarios for streamlining the computational drug discovery protocol. In computational disciplines, it has become common practice to share data and programming codes used for numerical calculations as to not only facilitate reproducibility, but also to foster collaborations (i.e. to drive the project further by introducing new ideas, growing the data, augmenting the code, etc.). It is therefore inevitable that the field of computational drug design would adopt an open approach towards the collection, curation and sharing of data/code.
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    Item type:Publication,
    Design, synthesis and evaluation of N 2 ,N 4 -diaminoquinazoline based inhibitors of phosphodiesterase type 5
    (2019-01-15)
    Pobsuk, Nattakarn
    ;
    Paracha, Tamkeen Urooj
    ;
    Chaichamnong, Nattiya
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    Salaloy, Nattapas
    ;
    Suphakun, Praphasri
    We describe the design, synthesis and evaluation of a series of N <sup>2</sup> ,N <sup>4</sup> -diaminoquinazoline analogs as PDE5 inhibitors. Twenty compounds were prepared and these were assessed in terms of their PDE5 and PDE6 activity, ex-vivo vasodilation response, mammalian cytotoxicity and aqueous solubility. Molecular docking was used to determine the binding mode of the series and this was demonstrated to be consistent with the observed SAR. Compound 15 was the most active PDE5 inhibitor (IC <inf>50</inf> = 0.072 ± 0.008 µM) and exhibited 4.6-fold selectivity over PDE6. Ex-vivo assessment of 15 and 22 in a rat pulmonary artery vasodilation model demonstrated EC <inf>50</inf> s of 1.63 ± 0.72 µM and 2.28 ± 0.74 µM respectively.