A series of nineteen substituted 1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3, 4-b]indoles analogues of neuroleptic drug, Centbutindole have been studied using quantitative structure-activity relationship analysis. The derived models display good fits to the experimental data (r>or=0.75) having good predictive power (r(cv)>or=0.688). The best model describes a high correlation between predicted and experimental activity data (r=0.967). Statistical analysis of the equation populations indicates that hydrophobicity (as measured by pi(R), logP(o/w) and SlogP_VSA8), dipole y and structural parameters in terms of indicator variable, (In(1)) and globularity are important variables in describing the variation in the neuroleptic activity in the series.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0968-0896(02)00652-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Improving Molecular Design with Direct Inverse Analysis of QSAR/QSPR Model.
Mol Inform
January 2025
Department of Applied Chemistry, School of Science and Technology, Meiji University, 1-1-1 Higashi-Mita, Tama-ku, Kawasaki, Kanagawa 214-8571, Japan.
Recent advances in machine learning have significantly impacted molecular design, notably the molecular generation method combining the chemical variational autoencoder (VAE) with Gaussian mixture regression (GMR). In this method, a mathematical model is constructed with X as the latent variable of the molecule and Y as the target properties and activities. Through direct inverse analysis of this model, it is possible to generate molecules with the desired target properties.
View Article and Find Full Text PDFDesign, Structure-Activity Relationships, and Computational Modeling Studies of a Series of α-Helix Biased, Ultra-Short Glucagon-like Peptide-1 Receptor Agonists.
Molecules
December 2024
Resolute Bio, 48 Dunham Rd., Suite 5400, Beverly, MA 01915, USA.
A systematic structure-activity and computational modeling analysis of a series of glucagon-like peptide-1 receptor (GLP-1R) agonists based upon an ultra-short GLP-1 peptide, H-His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Bip-Bip-NH2, was conducted. This highly potent 11-mer peptide led to a deeper understanding of the α-helical bias of strategic α-methylation within the linear parent template as well as optimization of GLP-1R agonist potency by 1000-fold. These data were correlated with previously reported co-structures of both full-length GLP-1 analogs and progenitor N-terminal GLP-1 fragment analogs related to such ultra-short GLP-1R agonist peptides.
View Article and Find Full Text PDFHarnessing the Power of Machine Learning Guided Discovery of NLRP3 Inhibitors Towards the Effective Treatment of Rheumatoid Arthritis.
Cells
December 2024
Department of Herbal Pharmacology, College of Korean Medicine, Gachon University, 1342 Seongnamdae-ro, Sujeong-gu, Seongnam-si 13120, Republic of Korea.
The NLRP3 inflammasome, plays a critical role in the pathogenesis of rheumatoid arthritis (RA) by activating inflammatory cytokines such as IL1β and IL18. Targeting NLRP3 has emerged as a promising therapeutic strategy for RA. In this study, a multidisciplinary approach combining machine learning, quantitative structure-activity relationship (QSAR) modeling, structure-activity landscape index (SALI), docking, molecular dynamics (MD), and molecular mechanics Poisson-Boltzmann surface area MM/PBSA assays was employed to identify novel NLRP3 inhibitors.
View Article and Find Full Text PDFDesign, synthesis, and biological evaluation of novel thiourea derivatives as small molecule inhibitors for prostate specific membrane antigen.
Bioorg Chem
January 2025
Department of Chemistry, Indian Institute of Technology Indore, Indore 453552 India; Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Indore 453552 India. Electronic address:
Prostate cancer (PCa) has emerged to be the second leading cause of cancer-related deaths in men. Molecular imaging of PCa using targeted radiopharmaceuticals specifically to PCa cells promises accurate staging of primary disease, detection of localized and metastasized tumours, and helps predict the progression of the disease. Glutamate urea heterodimers have been popularly used as high-affinity small molecules in the binding pockets of popular and well-characterized PCa biomarker, prostate specific membrane antigen (PSMA).
View Article and Find Full Text PDFIn-silico-based lead optimization of hit compounds targeting mitotic kinesin Eg5 for cancer management.
In Silico Pharmacol
January 2025
Phyto-medicine and Computational Biology Laboratory, Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State Nigeria.
Unlabelled: Lead optimization is vital for turning hit compounds into therapeutic drugs. This study builds upon a prior in silico research, where the hit compounds had better binding affinity and stability compared to a reference drug. Using a genetic algorithm, 12,500 analogs of the top compounds from the prior study were generated.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!