Comparative QSAR studies using HQSAR,CoMFA, and CoMSIA methods on cyclic sulfone hydroxyethylamines as BACE1 inhibitors |
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| Institution: | 1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China;2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210023, China;1. Pharmacy Department, Faculty of Chemistry, Pontificia Universidad Católica de Chile, Vicuña Mackenna 4860, Santiago, Chile;2. Departamento de Química Orgánica, Facultad de Química, Pontificia Universidad Católica de Chile, 702843, Santiago, Chile;3. Universidad Bernardo OHiggins, Laboratorio de Bionanotecnología, General Gana 1702, Santiago, Chile;4. Instituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Av. Gran Bretaña 1111, Playa Ancha, Valparaíso, Casilla 5030, Chile;5. Department of Endocrinology, School of Medicine, Pontificia Universidad Católica de Chile, Lira 85, 5th Floor, Santiago Centro 8330074, Santiago, Chile;6. Facultad de Ciencia, Universidad San Sebastián, Campus Los Leones, Lota 2465, Providencia 7510157, Santiago, Chile.;7. Endocannabinoid Research Group, Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Via Campi Flegrei 34, Napoli, Italy |
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| Abstract: | The inhibition of β-secretase (BACE1) is currently the main pharmacological strategy available for Alzheimer’s disease (AD). 2D QSAR and 3D QSAR analysis on some cyclic sulfone hydroxyethylamines inhibitors against β-secretase (IC50: 0.002–2.75 μM) were carried out using hologram QSAR (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods. The best model based on the training set was generated with a HQSAR q2 value of 0.693 and r2 value of 0.981; a CoMFA q2 value of 0.534 and r2 value of 0.913; and a CoMSIA q2 value of 0.512 and r2 value of 0.973. In order to gain further understand of the vital interactions between cyclic sulfone hydroxyethylamines and the protease, the analysis was performed by combining the CoMFA and CoMSIA field distributions with the active sites of the BACE1. The final QSAR models could be helpful in the design and development of novel active BACE1 inhibitors. |
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| Keywords: | BACE1 AD HQSAR CoMFA CoMSIA |
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