3D-QSAR and molecular docking studies of 4-methyl quinazoline derivatives as PI3Kα inhibitors

Zhou

et al. 2022

IJERPH

In this study, 16 PAHs were selected as the priority control pollutants to summarize their environmental metabolism and transformation processes, including photolysis, plant degradation, bacterial degradation, fungal degradation, microalgae degradation, and human metabolic transformation. Meanwhile, a total of 473 PAHs by-products generated during their transformation and degradation in different environmental media were considered. Then, a comprehensive system was established for evaluating the PAHs by-products’ neurotoxicity, immunotoxicity, phytotoxicity, developmental toxicity, genotoxicity, carcinogenicity, and endocrine-disrupting effect through molecular docking, molecular dynamics simulation, 3D-QSAR model, TOPKAT method, and VEGA platform. Finally, the potential environmental risk (phytotoxicity) and human health risks (neurotoxicity, immunotoxicity, genotoxicity, carcinogenicity, developmental toxicity, and endocrine-disrupting toxicity) during PAHs metabolism and transformation were comprehensively evaluated. Among the 473 PAH’s metabolized and transformed products, all PAHs by-products excluding ACY, CHR, and DahA had higher neurotoxicity, 152 PAHs by-products had higher immunotoxicity, and 222 PAHs by-products had higher phytotoxicity than their precursors during biological metabolism and environmental transformation. Based on the TOPKAT model, 152 PAH by-products possessed potential developmental toxicity, and 138 PAH by-products had higher genotoxicity than their precursors. VEGA predicted that 247 kinds of PAH derivatives had carcinogenic activity, and only the natural transformation products of ACY did not have carcinogenicity. In addition to ACY, 15 PAHs produced 123 endocrine-disrupting substances during metabolism and transformation. Finally, the potential environmental and human health risks of PAHs metabolism and transformation products were evaluated using metabolic and transformation pathway probability and degree of toxic risk as indicators. Accordingly, the priority control strategy for PAHs was constructed based on the risk entropy method by screening the priority control pathways. This paper assesses the potential human health and environmental risks of PAHs in different environmental media with the help of models and toxicological modules for the toxicity prediction of PAHs by-products, and thus designs a risk priority control evaluation system for PAHs.

Section: Resultsmentioning

confidence: 99%

Potential Toxicity Risk Assessment and Priority Control Strategy for PAHs Metabolism and Transformation Behaviors in the Environment

Zhou

et al. 2022

IJERPH

Phys. Chem. Chem. Phys.

“…The translocator comparative molecular force field method (Topomer CoMFA) is a 3D-QSAR method 21 that can predict and optimize the biological activity of compounds, proposed in 2004 by Crame et al 22 It is the product of topomer technology of the molecular descriptors combined with CoMFA. 23 The Topomer CoMFA model is easy and fast to operate during the modeling process, it can rationally establish the relationship between the structure and activity of compounds, and it accurately assesses the contribution value of each cleavage group, which is indispensable for the molecular screening work afterwards.…”

Section: Topomer Comfamentioning

confidence: 99%

Design of vilazodone-donepezil chimeric derivatives as acetylcholinesterase inhibitors by QSAR, molecular docking and molecular dynamics simulations

Guo,

Chang,

Tong

et al. 2024

“…In the context of developing future strategies for plasmodium falciparum resistance prevention, the use of 2D-QSAR, molecular docking and ADMET studies have become critical methods [11][12][13][14][15][16][17][18][19]. This objective is accomplished by performing molecular modeling on fifty-five quinoline, isoquinoline and quinazoline derivatives synthesized by Jean Guillon et al [20].…”

Section: Introductionmentioning

confidence: 99%

QSAR, molecular docking and ADMET studies of quinoline, isoquinoline and quinazoline derivatives against Plasmodium falciparum malaria

et al. 2022

Self Cite

With the aim of researching new antimalarial drugs, a series of quinoline, isoquinoline and quinazoline derivatives were studied against the Plasmodium falciparum CQ-sensitive and MQ-resistant strain 3D7 protozoan parasite.DFT with B3LYP functional and 6-311G basis set was used to calculate quantum chemical descriptors for QSAR models. The molecular mechanics (MM2) method was used to calculate constitutional, physicochemical, and topological descriptors. By randomly dividing the dataset into training and test sets, we were able to construct reliable models using linear regression (MLR), nonlinear regression (MNLR) and artificial neural networks (ANN). The determination coefficient values indicate the predictive quality of the established models. The robustness and predictive power of the generated models were also confirmed via internal validation, external validation, the Y-Randomization test and the applicability domain. Furthermore, molecular docking studies were conducted to identify the key interactions between the studied molecules and the PfPMT receptor's active site.The findings of this contribution study indicate that the antimalarial activity of these compounds against Plasmodium falciparum appears to be largely determined by four descriptors, i.e., Total Connectivity (Tcon), percentage of carbon (C (%)), density (D) and bond length between the two nitrogen atoms (Bond N-N).On the basis of the reliable QSAR model and molecular docking results, several new antimalarial compounds have been designed. The selection of drug-candidates was performed according to drug-likeness and ADMET parameters.