Browsing by Author "Bouachrine, Mohammed"

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    Identification of Novel Indole Derivatives as Potent ?-Amylase Inhibitors for the Treatment of Type-II Diabetes Using in-Silico Approaches
    (AMG Transcend Association, 2022-04-09T00:00:00) Khatabi, Khalil El; El-Mernissi, Reda; Hajji, Halima; Singh, Atul Kumar; Ajana, Mohammed Aziz; Lakhlifi, Tahar; Kumar, Shashank; Bouachrine, Mohammed
    The ?-amylase is regarded as a promising drug target for diabetes mellitus-type II. Hence, inhibiting ?-amylase activity is a potential drug discovery approach for treating this chronic metabolic disorder. The present study explores the structural requirements and understands the inhibition mechanism of the novel developed indole-based derivatives as ?-amylase inhibitors through 3D-QSAR, molecular docking, ADMET, and molecular dynamics (MD) simulation. The 3D-QSAR study showed good statistical reliability for two developed predictive models; CoMFA and CoMSIA. Through a deep investigation of docking analysis, detailed interactions with ?-amylase of the most active compound 7 were explored. Four new indole derivatives were designed based on the contour maps and docking analysis, with significantly higher inhibitory activity than the molecules in the dataset. The selected molecules were evaluated for pharmacokinetic properties, showing a reasonably good ADMET profile. Furthermore, a 20-ns MD simulation of selected compounds bound to ?-amylase was performed to ensure stability during simulation further. Greater stability of the designed molecule-protein complex A1 was found. The present findings shed light on the binding mode and the interactions between newly designed compounds, especially compound A1 and ?-amylase and may be beneficial for drug development efforts targeting type-II diabetes. � 2022 by the authors.
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    Novel Eubacterium rectale inhibitor from Coriandrum sativum L. for possible prevention of colorectal cancer: a computational approach
    (Taylor and Francis Ltd., 2022-10-20T00:00:00) El Khatabi, Khalil; Kumar, Shashank; El-Mernissi, Reda; Singh, Atul Kumar; Ajana, Mohammed Aziz; Lakhlifi, Tahar; Bouachrine, Mohammed
    This research aims to screen out the effective bioactive compounds from Coriander (Coriandrum sativum L.), which may be novel potential inhibitors of Eubacterium rectale for the prevention of colorectal cancer (CRC). A series of 8 coriander-derived chemical compounds previously assessed for their anti-inflammatory, antioxidant, and antidiabetic activities were tested against Carbohydrate ABC transporter substrate-binding protein and compared to the standard inhibitor Acarbose, to support their use as novel Eubacterium rectale inhibitors. Herein, these derivatives were submitted to a thorough analysis of docking studies, in which detailed interactions of the selected phytocompounds with carbohydrate ABC transporter substrate-binding protein were revealed. Molecular docking analysis recommends Rutin, Gallocatechin, and Epigallocatechin as the most potential Eubacterium rectale inhibitors among the eight selected phytochemical compounds. Subsequently, the stability of the three selected phytochemical complexes was checked using molecular dynamics (MD) simulation at 100 ns and Molecular Mechanics combined with Poisson-Boltzmann Surface Area (MM-PBSA). The results show quite good stability for Rutin and Gallocatechin. In silico ADMET prediction was performed on the selected compounds, and the findings revealed a reasonably good ADMET profile for both Rutin and Gallocatechin. The current findings predict that Gallocatechin could be a better CRC preventive natural compound, and, further in�vitro, in�vivo and clinical studies may confirm its therapeutic potential. Communicated by Ramaswamy H. Sarma. � 2022 Informa UK Limited, trading as Taylor & Francis Group.