SEARCH · PubMed Health

Results for “molecular docking studies”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources

PubMed2001

Synthesis and biological evaluation of all A-ring stereoisomers of 5,6-trans-2-methyl-1,25-dihydroxyvitamin D(3) and their 20-epimers: possible binding modes of potent A-ring analogues to vitamin D receptor.

BACKGROUND: The secosteroid 1 alpha,25-dihydroxyvitamin D(3) (1) has a wide variety of biological activities, which makes it a promising therapeutic agent for the treatment of cancer, psoriasis and osteoporosis. Insight into the structure-activity relationships of the A-ring of 1 is still needed to assist the development of more potent and selective analogues as candidate chemotherapeutic agents, as well as to define the molecular mode of action. RESULTS: All possible A-ring stereoisomers of 5,6-trans-2-methyl-1,25-dihydroxyvitamin D(3) (6a-h) and their 20-epimers (7a-h) were designed and efficiently synthesized. The dependence of the affinities for vitamin D receptor (VDR) and vitamin D binding protein (DBP), as well as the HL-60 cell differentiation-inducing activity, upon the stereochemistry of the A-ring and at C20 in the side chain was evaluated. CONCLUSIONS: The binding affinities and potency of the 5,6-trans and 5,6-cis analogues were enhanced by a 2-methyl substituent in a certain orientation. Molecular docking studies based upon the X-ray crystal structure of VDR suggested that the axial 2-methyl group would be accommodated in a pocket surrounded by hydrophobic amino acid residues in the ligand binding domain, resulting in enhanced interaction.

Animals↗

PubMed2006

Novel effect of C75 on carnitine palmitoyltransferase I activity and palmitate oxidation.

C75 is a potential drug for the treatment of obesity. It was first identified as a competitive, irreversible inhibitor of fatty acid synthase (FAS). It has also been described as a malonyl-CoA analogue that antagonizes the allosteric inhibitory effect of malonyl-CoA on carnitine palmitoyltransferase I (CPT I), the main regulatory enzyme involved in fatty acid oxidation. On the basis of MALDI-TOF analysis, we now provide evidence that C75 can be transformed to its C75-CoA derivative. Unlike the activation produced by C75, the CoA derivative is a potent competitive inhibitor that binds tightly but reversibly to CPT I. IC50 values for yeast-overexpressed L- or M-CPT I isoforms, as well as for purified mitochondria from rat liver and muscle, were within the same range as those observed for etomoxiryl-CoA, a potent inhibitor of CPT I. When a pancreatic INS(823/13), muscle L6E9, or kidney HEK293 cell line was incubated directly with C75, fatty acid oxidation was inhibited. This suggests that C75 could be transformed in the cell to its C75-CoA derivative, inhibiting CPT I activity and consequently fatty acid oxidation. In vivo, a single intraperitoneal injection of C75 in mice produced short-term inhibition of CPT I activity in mitochondria from the liver, soleus, and pancreas, indicating that C75 could be transformed to its C75-CoA derivative in these tissues. Finally, in silico molecular docking studies showed that C75-CoA occupies the same pocket in CPT I as palmitoyl-CoA, suggesting an inhibiting mechanism based on mutual exclusion. Overall, our results describe a novel role for C75 in CPT I activity, highlighting the inhibitory effect of its C75-CoA derivative.

4-Butyrolactone↗

PubMed2006

Taspine: bioactivity-guided isolation and molecular ligand-target insight of a potent acetylcholinesterase inhibitor from Magnolia x soulangiana.

A bioactivity-guided approach was taken to identify the acetylcholinesterase (AChE, EC 3.1.1.7) inhibitory agent in a Magnolia x soulangiana extract using a microplate enzyme assay with Ellman's reagent. This permitted the isolation of the alkaloids taspine (1) and (-)-asimilobine (2), which were detected for the first time in this species. Compound 1 showed a significantly higher effect on AChE than the positive control galanthamine and selectively inhibited the enzyme in a long-lasting and concentration-dependent fashion with an IC(50) value of 0.33 +/- 0.07 muM. Extensive molecular docking studies were performed with human and Torpedo californica-AChE employing Gold software to rationalize the binding interaction. The results suggested ligand 1 to bind in an alternative binding orientation when compared to galanthamine. While this is located in close vicinity to the catalytic amino acid triad, the 1-AChE complex was found to be stabilized by (i) sandwich-like pi-stacking interactions between the planar aromatic ligand (1) and the Trp84 and Phe330 of the enzyme, (ii) an esteratic site anchoring with the amino side chain, and (iii) a hydrogen-bonding network.

Alkaloids↗

PubMed2025

Click synthesis of some novel benzo[d]thiazole-1,2,3-triazole hybrid compounds with benzamide and/or benzoate tethers as EGFR-dependent signaling inhibitors against breast cancer.

The elaboration of anti-breast cancer agents targeting EGFR represents a promising strategy in medicinal chemistry. Consequently, under optimized Cu(i)-catalyzed click synthesis, a new library of 1,4-disubstituted 1,2,3-triazole-based benzo[d]thiazole scaffold carrying benzamide and/or benzoate tethers 5a-t was designed, synthesized, and characterized by appropriate spectral techniques. They were also screened for their in vitro anti-cancer activity against a panel of cancer cell lines, breast (T47D), prostate (PC3), lung (A549), and colon (HCT116) human cancer, along with normal fibroblast cells. Notably, the hybrid triazoles, 5p, 5s, and 5t emerged as the most potent candidates, especially against T47D, with IC50 values of 15, 26, and 28 μM, respectively. Compound 5p significantly induced apoptosis in T47D by 27.3-fold, causing total apoptosis of 19.39% compared to 0.71%, arresting cell proliferation at the G2/M phase. Regarding EGFR as the molecular target, among the tested compounds, 5p significantly inhibited EGFR by 96.8%, with an IC50 value of 65.6 nM, compared to erlotinib, having an IC50 value of 84.1 nM. Compound 5p showed promising PI3K/AKT/mTOR inhibition as the EGFR-dependent signaling pathway with IC50 values of 4.98 μM, 0.21 μM, and 0.49 nM, respectively, compared to their reference inhibitors. Finally, a molecular docking study highlighted the binding mode disposition and binding interactions with key amino acids as a promising EGFR inhibitor.

Journal Article↗

PubMed2001

Theoretical evidence of a salt bridge disruption as the initiating process for the alpha1d-adrenergic receptor activation: a molecular dynamics and docking study.

This study reports the building of the three-dimensional structure of the rat alpha1d-adrenergic receptor through a topology approach based on the structure of the rhodopsin receptor from cryoelectron microscopy. The validity and reliability of the receptor model were assessed through exhaustive molecular dynamics and docking studies. Some interesting ligand-receptor interactions were identified along with significant differences between the binding mode of agonists and antagonists. The importance of the disruption of a salt bridge as a possible initial event leading to receptor activation is discussed on the basis of data from mutagenesis and molecular dynamics studies.

Amino Acid Sequence↗

PubMed2003

Detailed analysis of grid-based molecular docking: A case study of CDOCKER-A CHARMm-based MD docking algorithm.

The influence of various factors on the accuracy of protein-ligand docking is examined. The factors investigated include the role of a grid representation of protein-ligand interactions, the initial ligand conformation and orientation, the sampling rate of the energy hyper-surface, and the final minimization. A representative docking method is used to study these factors, namely, CDOCKER, a molecular dynamics (MD) simulated-annealing-based algorithm. A major emphasis in these studies is to compare the relative performance and accuracy of various grid-based approximations to explicit all-atom force field calculations. In these docking studies, the protein is kept rigid while the ligands are treated as fully flexible and a final minimization step is used to refine the docked poses. A docking success rate of 74% is observed when an explicit all-atom representation of the protein (full force field) is used, while a lower accuracy of 66-76% is observed for grid-based methods. All docking experiments considered a 41-member protein-ligand validation set. A significant improvement in accuracy (76 vs. 66%) for the grid-based docking is achieved if the explicit all-atom force field is used in a final minimization step to refine the docking poses. Statistical analysis shows that even lower-accuracy grid-based energy representations can be effectively used when followed with full force field minimization. The results of these grid-based protocols are statistically indistinguishable from the detailed atomic dockings and provide up to a sixfold reduction in computation time. For the test case examined here, improving the docking accuracy did not necessarily enhance the ability to estimate binding affinities using the docked structures.

Algorithms↗

PubMed2006

Towards discovering dual functional inhibitors against both wild type and K103N mutant HIV-1 reverse transcriptases: molecular docking and QSAR studies on 4,1-benzoxazepinone analogues.

To find useful information for discovering dual functional inhibitors against both wild type (WT) and K103N mutant reverse transcriptases (RTs) of HIV-1, molecular docking and 3D-QSAR approaches were applied to a set of twenty-five 4,1-benzoxazepinone analogues of efavirenz (SUSTIVA), some of them are active against the two RTs. 3D-QSAR models were constructed, based on their binding conformations determined by molecular docking, with r(2)(cv) values ranging from 0.656 to 0.834 for CoMFA and CoMSIA, respectively. The models were then validated to be highly predictive and extrapolative by inhibitors in two test sets with different molecular skeletons. Furthermore, CoMFA models were found to be well matched with the binding sites of both WT and K103N RTs. Finally, a reasonable pharmacophore model of 4,1-benzoxazepinones were established. The application of the model not only successfully differentiated the experimentally determined inhibitors from non-inhibitors, but also discovered two potent inhibitors from the compound database SPECS. On the basis of both the 3D-QSAR and pharmacophore models, new clues for discovering and designing potent dual functional drug leads against HIV-1 were proposed: (i) adopting positively charged aliphatic group at the cis-substituent of C3; (ii) reducing the electronic density at the position of O4; (iii) positioning a small branched aliphatic group at position of C5; (iv) using the negatively charged bulky substituents at position of C7.

Drug Design↗

PubMed2006

Exploring the molecular basis of the enantioselective binding of penicillin G acylase towards a series of 2-aryloxyalkanoic acids: a docking and molecular dynamics study.

In the present paper, molecular modeling studies were undertaken in order to shed light on the molecular basis of the observed enantioselectivity of penicillin G acylase (PGA), a well known enzyme for its industrial applications, towards 16 racemic 2-aryloxyalkanoic acids, which have been reported to affect several biological systems. With this intention docking calculations and MD simulations were performed. Docking results indicated that the (S)-enantiomers establish several electrostatic interactions with SerB1, SerB386 and ArgB263 of PGA. Conversely, the absence of specific polar interactions between the (R)-enantiomers and ArgB263 seems to be the main reason for the different binding affinities observed between the two enantiomers. Results of molecular dynamics simulations demonstrated that polar interactions are responsible for both the ligand affinity and PGA enantiospecificity. Modeling calculations provided possible explanations for the observed enantioselectivity of the enzyme that rationalize available experimental data and could be the basis for future protein engineering efforts.

Alkanes↗

PubMed2005

Hypocrea jecorina (Trichoderma reesei) Cel7A as a molecular machine: A docking study.

Hypocrea jecorina (formerly Trichoderma reesei) Cel7A has a catalytic domain (CD) and a cellulose-binding domain (CBD) separated by a highly glycosylated linker. Very little is known of how the 2 domains interact to degrade crystalline cellulose. Based on the interaction energies and forces on cello-oligosaccharides computationally docked to the CD and CBD, we propose a molecular machine model, where the CBD wedges itself under a free chain end on the crystalline cellulose surface and feeds it to the CD active site tunnel. Enzyme-substrate interactions produce the forces required to pull cellulose chains from the surface and also to help the enzyme move on the cellulose chain for processive hydrolysis. The energy to generate these forces is ultimately derived from the chemical energy of glycosidic bond breakage.

Binding Sites↗

PubMed2006

Molecular docking-based study of vasopressin analogues modified at positions 2 and 3 with N-methylphenylalanine: influence on receptor-bound conformations and interactions with vasopressin and oxytocin receptors.

In this study, four cyclic vasopressin (CYFQNCPRG-NH(2), AVP) analogues substituted at positions 2 and 3 with four combinations of enantiomers of N-methylphenylalanine have been investigated. Three-dimensional structures of analogues have been formerly determined using NMR spectroscopy in dimethyl sulfoxide. Three-dimensional models of the vasopressin and oxytocin receptors were constructed by combining the multiple sequence alignment and the RD crystal structure as a template. The analogues have been docked into the receptor using the AutoDock program. The relaxation of the receptor-ligand complexes using energy minimization, followed by the constrained simulated annealing protocols (CSA), has been performed. The receptor-bound conformations of the investigated analogues have been proposed. We concluded that the N-methylated residues at positions 2 and 3 act as a structural restraint, determining the conformation of analogues, their location inside the receptor cavity, and mutual arrangement of the aromatic side chains. The conserved polar residues constitute the handles keeping the biologically active analogues inside the binding cavity. The Arg(8)-D(2.65) salt bridge might be responsible for analogue-selective binding in OTR and V1aR versus V2R, where the positively charged K(2.65) 100 is present at the equivalent position.

Amino Acid Sequence↗

PubMed2006

The betaI/betaIII-tubulin isoforms and their complexes with antimitotic agents. Docking and molecular dynamics studies.

Both microtubule destabilizer and stabilizer agents are important molecules in anticancer therapy. In particular, paclitaxel has been demonstrated to be effective for the treatment of ovarian, breast, and nonsmall cell lung carcinomas. It has been shown that emergence of resistance against this agent correlates with an increase in the relative abundance of tubulin isoform betaIII and that the more recently discovered IDN5390 can be effectively used once resistance has emerged. In this paper, we analyze the binding modes of these antimitotic agents to type I and III isoforms of beta-tubulin by computational methods. Our results are able to provide a molecular explanation of the experimental data. Using the same protocol, we could also show that no preference for any of the two isoforms can be detected for epothilone A, a potentially very interesting drug for which no data about the emergence of resistance is currently available. Our analysis provides structural insights about the recognition mode and the stabilization mechanism of these antimitotic agents and provides useful suggestions for the design of more potent and selective antimitotic agents.

Algorithms↗

PubMed2006

Docking studies of nickel-peptide deformylase (PDF) inhibitors: exploring the new binding pockets.

The binding modes of a series of known activity inhibitors docking to Peptide deformylase (PDF) have been studied using molecular docking software AutoDock3.0.5. In this study, good correlation (R(2)=0.894) between calculated binding energies and experimental inhibitory activities is obtained. We find that some shallow pockets near the known active pocket are very important which can accommodate the side-chains of the inhibitor. Moreover, a new binding pocket is also explored. All these may provide something useful for designing the potent inhibitors.

Amidohydrolases↗

PubMed2026

Analysis of the molecular mechanism underlying di(2-ethylhexyl) phthalate-induced bladder carcinogenesis via network toxicology and molecular docking approaches: An observational study.

This study aims to investigate the toxicity of di(2-ethylhexyl) phthalate (DEHP) and the potential molecular mechanisms of DEHP-induced bladder cancer (BLCA) using network toxicology and molecular docking strategies. The toxicity of DEHP was assessed using Prox-II software, and potential targets for DEHP-induced BLCA were identified by integrating data from ChEMBL database, Search Tool for Interactions of Chemicals, SwissTargetPrediction, GeneCards, Therapeutic Target Database, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas. STRING database and Cytoscape were employed to construct target networks and determine core targets. The expression levels of core targets were analyzed using R. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed on potential and core targets. Molecular docking was carried out using CB-Dock 2 to verify the interactions between DEHP and core targets. A total of 105 potential targets related to DEHP-induced BLCA were identified, from which 7 core targets were selected: cyclin-dependent kinase 1, interleukin 6, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, cyclin B2, and B-cell lymphoma 2. IL-6 and B-cell lymphoma 2 showed downregulated expression in tumor tissues, while cyclin-dependent kinase 1, cyclin-dependent kinase 2, cyclin B1, Erb-B2 receptor tyrosine kinase 2, and cyclin B2 were upregulated. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses indicated that these targets were enriched in cell signaling and cancer-related pathways. Molecular docking confirmed that DEHP interacts with these core targets. DEHP may promote the development of BLCA by interacting with key proteins and signaling pathways. This study provides a theoretical basis for understanding the molecular mechanisms of DEHP-induced BLCA and offers references for future prevention and treatment strategies.

Diethylhexyl Phthalate↗

PubMed2025

Network pharmacology-based study on the mechanism of Tangfukang formula against type 2 diabetes mellitus.

OBJECTIVE: To explore the mechanism of Tangfukang formula (, TFK) in treating type 2 diabetes mellitus (T2DM). METHODS: We employed network pharmacology combined with experimental validation to explore the potential mechanism of TFK against T2DM. Initially, we filtered bioactive compounds with the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Symptom Mapping (SymMap), and gathered targets of TFK and T2DM. Subsequently, we constructed a protein-protein interaction (PPI) network, enriched core targets through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and adopted molecular docking to study the binding mode of compounds and the signaling pathway. Finally, we employed a KKAy mice model to investigate the effect and mechanism of TFK against T2DM. Biochemical assay, histology assay, and Western blot (WB) were used to assess the mechanism. RESULTS: There were 492 bioactive compounds of TFK screened, and 1226 overlapping targets of TFK against T2DM identified. A compound-T2DM-related target network with 997 nodes and 4439 edges was constructed. KEGG enrichment analysis identified some core pathways related to T2DM, including adenosine 5-monophosphate-activated protein kinase (AMPK) signaling pathway. Molecular docking study revealed that compounds of TFK, including citric acid, could bind to the active pocket of AMPK crystal structure with free binding energy of －4.8, －8 and －7.9, respectively. Animal experiments indicated that TFK decreased body weight, fasting blood glucose, fasting serum insulin, homeostasis model of insulin resistance, glycosylated serum protein, total cholesterol, triglyceride, and low-density lipoprotein cholesterol, and improve oral glucose tolerance test results. TFK reduced steatosis in liver tissue, and infiltration of inflammatory cells, and protected liver cells to a certain extent. WB analysis revealed that, TFK upregulated the phosphorylation of AMPK and branched-chain α-ketoacid dehydrogenase proteins. CONCLUSION: TFK has the potential to effectively manage T2DM, possibly by regulating the AMPK signaling pathway. The present study lays a new foundation for the therapeutic application of TFK in the treatment of T2DM.

Diabetes Mellitus, Type 2↗

PubMed2026

Exploring the mechanism of the Lianshi Jianpi formula in treating impaired glucose tolerance: a network pharmacology, molecular docking, and experimental validation study.

OBJECTIVE: To explore the bioactive constituents, key targets, signalling pathways, and molecular mechanisms of Lianshi Jianpi formula (, LSJPF) in the treatment of impaired glucose tolerance (IGT) through network pharmacology, molecular docking, and in vivo experiments. METHODS: The active ingredients and targets of LSJPF were identified using the Traditional Chinese Medicine Systems Pharmacology and HERB databases, whereas the IGT-related targets were sourced from GeneCards, DisGeNET, and PubMed. The overlap analysis identified potential targets of LSJPF. Protein-protein interaction networks and core targets were evaluated using the Search Tool for the Retrieval of Interacting Genes/Proteins and Cytoscape, and molecular docking confirmed the binding affinities. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using Metascape. The therapeutic mechanisms were validated in an animal IGT model. RESULTS: LSJPF contained 229 compounds, with 15 active compounds and 77 potential target proteins. The phosphatidylinositol-3-kinase (PI3K)-protein kinase B (AKT) signalling pathway emerged as a key IGT pathway. The KEGG enrichment analysis revealed the pivotal genes RAC-alpha serine/threonine-protein kinase (AKT1), heat shock protein 90 kDa alpha B1, and B-cell lymphoma 2 family protein, which predominantly interact with beta-sitosterol and beta-carotene, the major constituents of Semen Euryales, Semen lablab Album, Semen sojae Atricolor in LSJPF. Molecular docking revealed strong binding affinities between LSJPF and IGT-related targets. In an animal IGT model, LSJPF treatment prevented weight loss; reduced food and water intake; decreased blood glucose levels; improved insulin resistance; decreased serum triglyceride, cholesterol, and low-density lipoprotein cholesterol levels; alleviated liver pathology; and significantly increased the levels of phosphorylated adenosine 5'-monophosphate-activated protein kinase (AMPK), PI3K, and AKT, suggesting its potential role in regulating glucose and lipid metabolism. CONCLUSIONS: These findings reveal the potential of LSJPF as an IGT intervention that targets the AMPK/PI3K/AKT cascade, validating network pharmacology predictions and highlighting the role of multipathway mechanisms in metabolic diseases.

Molecular Docking Simulation↗

PubMed2026

Multitarget interactions of bisphenol A in polycystic ovary syndrome: evidence from integrated network toxicology, mendelian randomization, and molecular docking.

OBJECTIVE: To study the potential pathogenic mechanisms of bisphenol A (BPA) in polycystic ovary syndrome (PCOS) using an integrative computational strategy. DESIGN: Integrative computational study combining network toxicology, Mendelian randomization (MR), and molecular docking. SUBJECTS: For MR analysis, genetic data were sourced from large European-ancestry cohorts, including plasma protein quantitative trait loci data and genome-wide association study summary statistics for PCOS (3,045 cases and 267,780 controls). EXPOSURE: In silico exposure to BPA for target prediction; genetically predicted plasma protein levels for causal inference. MAIN OUTCOME MEASURES: Identification of overlapping targets between BPA and PCOS; functional enrichment pathways; causal effects of prioritized proteins on PCOS risk (odds ratios with 95% confidence intervals); binding affinities between BPA and core targets (kcal/mol). RESULTS: Network toxicology identified 310 overlapping targets between BPA and PCOS. Enrichment analyses revealed significant involvement in endocrine signaling, inflammatory pathways (eg, IL-17), and cellular processes. MR demonstrated that genetically elevated levels of RET, CXCL8, HTR6, MMP1, MMP9, NTRK1, and TNNI2 were significantly associated with increased PCOS risk, whereas higher PSAP and SHBG levels were protective. Molecular docking confirmed stable binding between BPA and all nine key targets, with strongest affinity for SHBG (-8.4 kcal/mol), followed by NTRK1, TNNI2, and RET. CONCLUSION: This integrative investigation suggests that BPA may contribute to PCOS pathogenesis through multitarget interactions involving inflammatory mediators, endocrine regulators, and tissue remodeling proteins. The findings provide prioritized targets and mechanistic insights for future experimental validation and environmental risk assessment.

Female↗

PubMed2003

Design, synthesis and evaluation of bifunctional inhibitors of type II dehydroquinase.

Inhibitors of type II dehydroquinase were designed to straddle the two distinct binding sites identified for the inhibitor (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid and a glycerol molecule in a crystallographic study of the Streptomyces coelicolor enzyme. A number of compounds were designed to incorporate characteristics of both ligands. These analogues were synthesized from quinic acid, and were assayed against type I (Salmonella typhi) and type II (S. coelicolor) dehydroquinases. None of the analogues showed inhibition for type I dehydroquinase. Six of the analogues were shown to have inhibition constants in the micromolar to low millimolar range against the S. coelicolor type II dehydroquinase, while two showed no inhibition. The binding modes of the analogues in the active site of the S. coelicolor enzyme were studied by molecular docking with GOLD1.2. These studies suggest a binding mode where the ring is in a similar position to (1S,3R,4R)-1,3,4-trihydroxy-5-cyclohexene-1-carboxylic acid in the crystal structure and the side-chain occupies part of the glycerol binding-pocket.

Binding Sites↗

PubMed2002

Computer-aided design of selective COX-2 inhibitors: comparative molecular field analysis, comparative molecular similarity indices analysis, and docking studies of some 1,2-diarylimidazole derivatives.

Comparative molecular field analysis and comparative molecular similarity indices analysis were performed on 114 analogues of 1,2-diarylimidazole to optimize their cyclooxygenase-2 (COX-2) selective antiinflammatory activities. These studies produced models with high correlation coefficients and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of both COX-1 and COX-2 to analyze the receptor ligand interactions that confer selectivity for COX-2. The most active molecule in the series (53) adopts an orientation similar to that of SC-558 (4-[5-(4-bromophenyl)-3-trifluoromethyl-1H-1-pyrozolyl]-1-benzenesulfonamide) inside the COX-2 active site while the least active molecule (101) optimizes in a different orientation. In the active site, there are some strong hydrogen-bonding interactions observed between residues His90, Arg513, and Phe518 and the ligands. Additionally, a correlation of the quantitative structure-activity relationship data and the docking results is found to validate each other and suggests the importance of the binding step in overall drug action.

Binding Sites↗