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Inventi Rapid - Molecular Modeling

Articles

  • Inventi:pmm/25754/18
    IN-SILICO PHARMACOKINETICS PREDICTIONS OF 10,13-DIMETHYL-6-METHYLHEPTAN-2-YL)-TETRADECAHYDRO-1H-CYCLOPENTA[A] PHENANTHREN-3-YL) DERIVATIVES
    Tomy Muringayil Joseph*, Debarshi Kar Mahapatra

    In the previous research done, the anti-inflammatory perspectives of the 10,13-dimethyl-6-methylheptan-2-yl)-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) derivatives; (R,3E,7E)-((3R,10R,13R,14R)-10,13-dimethyl-17-((S)-6-methylheptan -2-yl)- 2,3,4,7,8,9,10,11,12,13,14,15,16,17- tetradecahydro-1 H-cyclopenta[a]phenanthren-3-yl)-5-hydroxy-3-methyl-9-methyleneundeca-3,7-dienoate (1) and (E)-((3R,10R,13R,14R)-10,13-dimethyl-17-((S)-6-methylheptan-2-yl)-2,3,4,7,8, 9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)-6-oxooct-4-enoate (2) as cyclooxygenase -2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors have been studied by docking approach using the GLIDE module of Maestro 9.1 software. In the continued research, the pharmacokinetic perspectives were studied to ensure that the drug will produce intended action without compromise in the bioavailability. By employing the QikProp module of the Maestro 9.1, the essential pharmacokinetic properties of both the compounds were studied exhaustively. The observed predicted parameters indicated that the molecules have quite compromised pharmacokinetics and are relatively toxic to cardiac tissues. The serum protein binding was found to be very high and the amount of free drug will be very low. The very high value of log P was detected and the molecules violated both the Lipinski Rule of 5 and Jorgensen Rule of 3. However, the predicted oral absorption was seen to be 100%, which is relatively noteworthy for exhibiting oral bioavailability. In addition to it, high values of Apparent MDCK and Apparent Caco-2 influence over the transporters and metabolic processes (Phase II conjugation enzymes) and also represented enhanced human intestinal absorption. The present study indicated that the further rational design of the molecules is required which will lead to better development of these analogs as drug moieties.

    How to Cite this Article
    Tomy Muringayil Joseph, Debarshi Kar Mahapatra. In-silico Pharmacokinetics Predictions of 10, 13- dimethyl-6-methylheptan-2 -yl) -tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl) Derivatives. Inventi Rapid: Molecular Modeling, 2018(3):1-3, 2018.
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