Topological Surface Area Research Articles

DFT Calculations, Pro-Apoptotic Effects, and Anti-Infective Investigations of Alkaloids Isolated from the Stem Bark Extract of Enantia chlorantha

Fractionation of the stem bark of Enantia chlorantha Oliv yields three alkaloids, palmatine (1), jatrorrhizine (2), columbamine (3), and β-Sitosterol (4). In this investigation, density functional theory (DFT) calculations were carried out to evaluate the electronic structure and properties of 1–4 by DFT-B3LYP/6-31G level of theory using Gaussian 09 software. The highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), HOMO-LUMO energy difference (band gap), hardness (η), softness (S), dipole moment (μ), electronegativity (χ), hydrophobicity (logP), topological surface area (TPSA), and energy gap (Eg) were calculated. The in vitro cytotoxicity of the compounds was investigated against MCF-7 and HCT116 cancer cell lines using Wi-38 cells as a control. The compounds inhibited the proliferation of the MCF-7 and HCT116 cell lines and induced apoptosis via upregulation of caspase-3, Bax, PARP cleavage, and downregulation of Bcl-2. DFT analyses revealed that compounds 1 and 3 have smaller energy gaps, 0.072 and 0.071eV, respectively, with the highest dipole moments; hence, these compounds are more chemically reactive and exhibit better modulation of caspase-3 enzyme and inhibitory activities of the MCF-3 and HCT116 cell lines. The antimicrobial and antiparasitic evaluation of 1–4 showed moderate efficacy against the bacterial strains and moderate antiparasitic activity against Cichlidogyrus tilapia.

Identifying potential inhibitors of C-X-C motif chemokine ligand10 against vitiligo: structure-based virtual screening, molecular dynamics simulation, and principal component analysis

The research aims to envisage small molecule inhibitors targeting the C-X-C motif chemokine ligand 10 (CXCL10) of the JAK/STAT pathway. CXCL10 plays a significant role in inducing auto-immunity in vitiligo through JAK/STAT pathway. To accomplish the aim, structure-based virtual screening with fundamental search limits, e.g., molecular weight (MW ≤ 500 Da), hydrogen bond donor (HBD ≤ 5), hydrogen bond acceptor (HBA ≤ 10), and lipophilicity (logP ≤ 5) was used to screen investigational molecules from MCULE database. The SBVS-ligand hits were sifted through toxicity profiling followed by filtration through the Brain or IntestinaL EstimateD-Egg model to check the human intestinal abortion and blood-brain barrier permeation based on two physicochemical properties, including topological surface area and WLOGP. The BOILED-Egg filtered compounds were passed through drug-likeness features other than Pfizer’s Lipinski rule of five, viz., Ghose filters, Muegge filters, Egan parameters, and Veber filters, followed by medicinal chemistry’s pan assay interference structure and Brenk alert investigation. Chemical compounds that comply with the above ADME descriptors were docked with target protein CXCL10 via AutoDock Vina. The stability of the top two ligand hits was assessed through dynamics simulations of 100 ns and principal component analysis and compared with the reference drugs Baicalein and EGCG. Based on the findings of Gibbs free energy of binding, ADME profiling, medicinal chemistry attributes depiction, root-mean-square deviation, root-mean-square fluctuation, solvent accessible surface area, the free energy of solvation, the radius of gyration, and PCA, MCULE2726078782-0-2 was found better than potential reference drug Baicalein. Communicated by Ramaswamy H. Sarma

Facile synthesis of platinum-copper aerogels for the oxygen reduction reaction

Although carbon-supported platinum (Pt/C) has been generally used as a catalyst for the oxygen reduction reaction (ORR) in fuel cells, its practical application is limited by the corrosion reaction of the carbon support. Therefore, it is essential to develop new self-supported catalysts for the ORR. Noble metal aerogels represent highly promising self-supported catalysts with large specific surface area and excellent electrocatalytic activity. Classic sol-gel processes for aerogel synthesis usually take days due to the slow gelation kinetics. Here, we report a straightforward strategy to synthesize platinum-copper (PtCu) aerogels by reducing the metal salt solution with an excess of sodium borohydride at room temperature. The PtCu aerogels are formed in a relatively short time of 1 h through a rapid nucleation mechanism. The obtained PtCu aerogels have a highly porous structure with an appreciable topological surface area of 33.0 m2/g and mainly exposed (111) facets, which are favorable for the ORR. Consequently, the PtCu aerogels exhibit excellent ORR activity with a mass activity of 369.4 mA/mgPt and a specific activity of 0.847 mA/cm2, which are 2.6 and 3.3 times greater than those of Pt/C, respectively. The PtCu aerogels show remarkable ORR catalysis among all the noble metal aerogels that have been reported. The porous morphology and outstanding electrocatalytic activities of the PtCu aerogels illustrate their promising applications in fuel cells.

Diversity matters: Widening the chemical space in organic solvent nanofiltration

Niche membrane technologies, such as organic solvent nanofiltration (OSN), offer considerable energy and operation cost reduction compared with conventional separation methods. However, despite their many advantages, their industrial implementation is hindered by small and specialized datasets, which hinders the development of more advanced prediction methods. In this study, we developed a medium-throughput system (MTS) for OSN with high robustness and low error. The MTS was used to generate a dataset containing 336 different molecules, and their rejection values were measured at two different pressures using three commercial DuraMem polyimide membranes with different molecular weight cut-off values in methanol. The diversity of the generated dataset was compared with the diversity values of other relevant datasets using 26 different chemometric molecular descriptors, including the heteroatom count, topological surface area, different shape descriptors, Van der Waals volume, logP, and logS. The rejection was found to be weakly dependent on the functional group and molecular weight at the lower end of the nanofiltration range. We proposed the use of a novel structural similarity-based indexing method for comparing solutes. Also, we established the first open-access and searchable dataset for OSN rejection values. The newly established www.osndatabase.com pilot website acts as the foundation of the dataset.

Clathriketal, a new tricyclic spiroketal compound from marine sponge Clathria prolifera attenuates serine exopeptidase dipeptidyl peptidase-IV

An undescribed tricyclic spiroketal compound clathriketal was purified from the solvent extract of the Microcionidae sponge Clathria prolifera, and was characterised as 7-(hydroxymethyl)-13-methoxy-3,11-dimethyl-4-oxo-octahydrospiro[chromene-9,13-pyran]-11-yl propionate by spectroscopic experiments. Clathriketal exhibited significant anti-hyperglycemic property by attenuating serine protease dipeptidyl peptidase-IV (IC50 0.37 mM), and its activity was comparable with the standard diprotin A (IC50 0.31 mM). The spiroketal also exhibited significant inhibitory potentials against carbolytic enzymes α-glucosidase (IC50 0.43 mM) and α-amylase (IC50 0.41 mM). Superior antioxidant properties of clathriketal against the oxidants, 2, 2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid and 2, 2-diphenyl-1-picrylhydrazyl (IC50 ∼1.2 mM) also reinforced its promising anti-hyperglycemic activity. Considerably greater topological surface area (91.29) coupled with lesser steric parameters of clathriketal, as elucidated from the structure-activity relationship analyses could further ascribe the improved ligand-receptor interactions resulting in its prospective anti-hyperglycemic activity. Molecular docking analysis of clathriketal with dipeptidyl peptidase-IV recorded lesser binding energy (–9.63 kcal/mol), which further corroborated its prospective antihyperglycemic activity.

Synthesis, Docking Study And In Vitro Anticancer Evaluation Of New Derivatives Of 2-(1-(2-Flouro-[1,1-Biphenyl]-4-Yl)Ethyl)-6-(Substituted Phenyl) Imidazole[2,1-B][1,3,4]Thiadiazole Derived From Flurbiprofen

Objectives: New derivatives of 2-(1-(2-flouro-[1,1-biphenyl]-4-yl)ethyl)-6-(substituted phenyl) imidazole[2,1-b][1,3,4]thiadiazole, compounds(2-5), were designed and synthesized from the starting parent molecule, flurbiprofen. Materials and Methods: Compound (1) was synthesized by refluxing flurbiprofen, as a starting material , with phosphorus oxychloride (POCl3), and thiosemicarbazide, resulting in flurbiprofen -1,3,4 thiadiazole -2 amine derivative. The target compounds(2-5) were obtained by refluxing compound(1) with different substituted phenacyl bromides, Results: The new compounds were characterized by FTIR, 1HNMRs and CHNS analysis. A molecular docking study of the synthesized compounds (2-5) against HIV protease indicated such compounds occupied the critical site of HIV protease pocket, and demonstrated excellent positioning of the compounds in the pocket. The best binding energy values were (-7.49, -7.22 , -7.51 and-7.12 kcal/mol) for the compounds (2 -5(, respectively. The anticipated physio-chemical parameters(calculated logarithmic of partition cofficent(Clog p),molecular volume (MV), number of violations (nviol), topological surface area (TPSA), and percent of absorption(%Abs.) were computed using software Molinspiration. In vitro outcomes, the target compounds were assessed by cell line study for their anticancer effects. All the tested compounds showed the most plausible anticancer activity, when compared to a positive control (atazanavir), using MTT cytotoxic assay, against human prostatic tumor (PC-3), glioma cell line (LN68), and normal WRL-68 cell line. Conclusion: The results revealed that compounds 2,3,4 and 5 exhibited the highest inhibitory activity against PC3 cell line at IC50 concentrations of 178.2, 75.09, 129.3and 110.5μg/mL, respectively, and they had moderate effects against LN299 cell line at IC50 concentrations 203,172.5, 169,and 157.7 μg/mL, respectively, compared to atazanavir, as a positive control against PC-3, at IC50, 157.3 μg/mL, and in LN299, at IC50 195.7 μg/mL. Also compound (5) attributed to cell-cycle arrest, and induction of apoptosis. The target compounds could be considered as promising as potential anticancer drugs.

Synthesis of Lapachol and 4-Hydroxyquinazoline Derivatives as Candidates for Antimalarial Activity

Malaria is a disease that still plagues many tropical countries, affecting around 228 million people and with approximately 430 thousand deaths worldwide. The resistance of the causative protozoan against the existing antimalarials has been increasing, including for combination therapies based on artemisinin, a first-line treatment against malaria. Therefore, the search for new antimalarial agents becomes essential. Lapachol and febrifugine are substances with antimalarial activity with the potential for the development of new antimalarials, but with relevant cytotoxicity. In this work, we propose the synthesis of two derivatives, one from lapachol and the other from febrifugine, aiming at an improvement in antimalarial activity and a decrease in cytotoxicity. Lapachol was isolated from the sawdust of purple ipe and derivatized in a twostep synthesis, providing an unprecedented derivative in 25% yield overall. The febrifugine derivative was synthesized from 4-hydroxyquinazoline in 61% yield (2 steps). Both were purified by column chromatography and characterized by 1 H, 13 C NMR, HSQC and HMBC. Also, the parameters as clogP, the presence of atoms capable of acting as acceptors or donors of hydrogen bonds, molecular mass, topological surface area, rotatable bonds were determined in order to predict the solubility and bioavailability of this compounds as drug candidates. DOI: http://dx.doi.org/10.17807/orbital.v12i4.1541

Callypyrones from marine Callyspongiidae sponge Callyspongia diffusa: antihypertensive bis-γ-pyrone polypropionates attenuate angiotensin-converting enzyme

Angiotensin I-converting enzyme (ACE) catalyses the biosynthesis of angiotensin II, a potent blood vessel constrictor, from angiotensin I, and ACE inhibitors were recognised as medications for hypertension. Undescribed bis-γ-pyrone polypropionate compounds, callypyrones A and B were purified from the organic extract of Callyspongiidae sponge species Callyspongia diffusa by repeated chromatographic purification. Callypyrone A exhibited significantly greater attenuation potential against ACE (IC50 0.48 mM) than that displayed by callypyrone B (IC50 0.57 mM) and showed comparable activity with standard ACE inhibitor captopril (IC50 0.36 mM). Higher electronic parameters of callypyrone A (topological surface area of 108.36) combined with balanced hydrophilic-lipophilic parameter (octanol–water coefficient, log P ow 1.9), as deduced from the structure–activity relationship analyses, could further indicate the improved ligand–receptor interactions resulting in its prospective ACE inhibitory activity. In silico docking analyses of the callypyrones with ACE recorded lowest binding energy (–12.58 kcal mol−1) for callypyrone A, which further supported the antihypertensive potential of the compound.

Screening of Therapeutic Agents for COVID-19 Using Machine Learning and Ensemble Docking Studies.

The current pandemic demands a search for therapeutic agents against the novel coronavirus SARS-CoV-2. Here, we present an efficient computational strategy that combines machine learning (ML)-based models and high-fidelity ensemble docking studies to enable rapid screening of possible therapeutic ligands. Targeting the binding affinity of molecules for either the isolated SARS-CoV-2 S-protein at its host receptor region or the S-protein:human ACE2 interface complex, we screen ligands from drug and biomolecule data sets that can potentially limit and/or disrupt the host–virus interactions. Top scoring one hundred eighty-seven ligands (with 75 approved by the Food and Drug Administration) are further validated by all atom docking studies. Important molecular descriptors (2χn, topological surface area, and ring count) and promising chemical fragments (oxolane, hydroxy, and imidazole) are identified to guide future experiments. Overall, this work expands our knowledge of small-molecule treatment against COVID-19 and provides a general screening pathway (combining quick ML models with expensive high-fidelity simulations) for targeting several chemical/biochemical problems.

Analysis on biological importance of antiseptic drug, O-Benzyl hydroxylamine, by the application of spectroscopic and theoretical tools

Biological importance of antiseptic drug; O-Benzyl hydroxylamine was explored using QSAR studies for ultimate usage for treating fungal infections. In this research work, the molecular spectroscopic tool and theoretical calculation method of analysis. The data acquired from both tools were evaluated and compared to validate structural and vibrational characteristics. Mulliken charge displacement around molecular site in order for exploring electronic properties to find out the cause of inducement of drug potential. The Lipinski rule of five was evaluated for the measurement of biological importance of the drug compound. The lipophilicity and topological surface area of the drug was monitored for determining biological process activity. The partial involvement of compositional bonds of the molecule was appraised for influential vibrational characteristics. The chemical environment for making chemical property was monitored from the uniform and asymmetrical chemical shift of core and allied carbons. The resultant oscillating potential orientation in the molecular site was identified and the residing zones were recognized to find out the origin of drug potential. The occurrence of CT complex process was studied and the CTC was found to be CC and C–N for generating drug activeness. The enhancement of hyper active polarization was measured in first and second order from which the charge level pulling on different entities were observed for ensuring the biological affinity of the compound. The enantiomer characteristics were thoroughly studied to measure the level of toxicity.

Machine Learning Derived Quantitative Structure Property Relationship (QSPR) to Predict Drug Solubility in Binary Solvent Systems

Prediction of drug solubility is a crucial problem in pharmaceutical industries for both drug delivery and discovery purposes. Several theoretical approaches have been proposed to predict drug solubility in mixed solvent systems when the solubility values in pure solvents are known. Quantitative structure property relationship (QSPR) approaches are gaining attention to predict various physical properties due to their robustness and computational tractability. In this work, a machine learning based QSPR approach is proposed to predict drug solubility in binary solvent systems using structural features, such as molar refractivity, McGowan volume, topological surface area, and so forth. A genetic algorithm based feature selection procedure is used to check the dependency between the selected features and to obtain the final set of significant features. Initially, solubility is assumed to behave linearly with respect to the structural features and model parameters are estimated using ordinary least-squares an...

α-Sulfonamidophosphonates as new anti-mycobacterial chemotypes: Design, development of synthetic methodology, and biological evaluation

Tuberculosis (TB) is the leading cause of death worldwide due to bacterial infection. The scarcity of effective drugs to treat the disease and the compounded problems due to the development of resistance to the available therapeutics and TB-HIV synergism drive medicinal chemists to search for new anti-Mtb chemotypes. Towards this endeavor, the α-sulfonamidophosphonate moiety has been identified as new anti-Mtb chemotype through the scaffold hopping as the design strategy, development of an effective synthetic methodology using green chemistry tools, and evaluation of anti-TB activity of the synthesized compounds against Mtb (Mycobacterium tuberculosis) H37Rv. Out of the sixteen compounds, five have been found to have MIC values of 1.56 μg/mL and one 3.125 μg/mL. The five most active compounds are non-cytotoxic to RAW 264.7 (mouse leukemic monocyte macrophage) cell lines. The compounds are found to possess acceptable values of the various parameters for drug likeness in accordance with the Lipinski rule with the topological surface area (tPSA) of >70 that suggest eligibility of these new molecular entities for further consideration as potential drug candidates.

Oximes short-acting CB1 receptor agonists

New oximes short-acting CB1 agonists were explored by the introduction of an internal oxime and polar groups at the C3 alkyl tail of Δ8-THC. The scope of the research was to drastically alter two important physicochemical properties hydrophobicity (log P) and topological surface area (tPSA) of the compound, which play a critical role in tissue distribution and sequestration (depot effect). Key synthesized analogs demonstrated sub-nanomolar affinity for CB1, marked reduction in hydrophobicity (ClogP∼2.5–3.5 vs 9.09 of Δ8-THC-DMH), and found to function as either agonists (trans-oximes) or neutral antagonists (cis-oximes) in a cAMP functional assay. All oxime analogs showed comparable affinity at the CB2 receptor, but surprisingly they were found to function as inverse agonists for CB2. In behavioral studies (i.e. analgesia, hypothermia) trans-oxime 8a exhibited a predictable fast onset (∼20 min) and short duration of pharmacological action (∼180 min), in contrast to the very prolonged duration of Δ8-THC-DMH (>24 h), thus limiting the potential for severe psychotropic side-effects associated with persistent activation of the CB1 receptor. We have conducted 100 ns molecular dynamic (MD) simulations of CB1 complexes with AM11542 (CB1 agonist) and both trans-8a and cis-8b isomeric oximes. These studies revealed that the C3 alkyl tail of cis-8b orientated within the CB1 binding pocket in a manner that triggered a conformational change that stabilized the CB1 receptor at its inactive-state (antagonistic functional effect). In contrast, the trans-8a isomer’s conformation was coincided with that of the AM11542 CB1 agonist-bound structure, stabilizing the CB1 receptor at the active-state (agonistic functional effect). We have selected oxime trans-8a based on its potency for CB1, and favorable pharmacodynamic profile, such as fast onset and predictable duration of pharmacological action, for evaluation in pre-clinical models of anorexia nervosa.

Synthesis and Characterization of Pyridine Compounds for Amperometric Measurements of Leukocyte Esterase

We introduce a new class of substrates (compounds I-III) for leukocyte esterase (LE) that react with LE yielding anodic current in direct proportion to LE activity. The kinetic constants Km and kcat for the enzymatic reactions were determined by amperometry at a glassy carbon electrode. The binding affinity of I-III for LE was two orders of magnitude better than that of existing optical LE substrates. The specificity constant kcat /Km was equal to 2.7, 3.8, and 5.8×105 m-1 s-1 for compounds containing the pyridine (I), methoxypyridine (II), and (methoxycarbonyl)pyridine (III), respectively, thus showing an increase in catalytic efficiency in this order. Compound III had the lowest octanol/water partition coefficient (log p=0.33) along with the highest topological surface area (tPSA=222 Å2 ) and the best aqueous solubility (4.0 mg mL-1 ). The average enzymatic activity of LE released from a single leukocyte was equal to 4.5 nU when measured with compound III.

Role of surface phenomena in concentrating incompatible elements: Au in pyrite from hydrothermal clays at thermal fields in southern Kamchatka

The paper reports data on pyrite obtained using microscopic, physicochemical, and analytical techniques. The major mineral concentrating Au in clays at the Upper Koshelevskoe and East Pauzhetka hydrothermal fields is pyrite, which contains Au evenly distributed in its crystals (0.07–0.25 ppm) and Au bound to the surface of its crystals (0.8–6.8 ppm). The clear correlations between the concentration of equally distributed Au and the topological surface area of single crystals and the absence of correlations with the bulk specific BET surface area rule out purely adsorption mechanisms of Au accommodation at the surface of pyrite crystals, because otherwise the concentration of the minor element would have been proportional to the actual surface area but not the geometric one. In contrast to what is typical of high-temperature hydrothermal systems, at hydrothermal fields Au is an element highly compatible with pyrite. This may be explained by changes in the growth mechanisms of pyrite crystals and the transition to their growth via incorporation of colloid and subcolloid particles. Low-temperature pyrite in hydrothermal clays exhibits certain geochemical features important for exploration for gold deposits related to modern and ancient hydrothermal systems. This pyrite differs from higher temperature pyrite at ancient gold deposits in bearing sulfoxide sulfur species on the surface of its crystals instead of monosulfide species and also in having a less ordered and dense structure, higher porosity, and a globular topography of the surface of crystals.

Monitoring Drug Self-Aggregation and Potential for Promiscuity in Off-Target In Vitro Pharmacology Screens by a Practical NMR Strategy

A simple NMR assay was applied to monitor the tendency of compounds to self-aggregate in aqueous media. The observation of unusual spectral trends as a function of compound concentration appears to be signatory of the formation of self-assemblies. (1)H NMR resonances of aggregating compounds were sensitive to the presence of a range of molecular assemblies in solution including large molecular-size entities, smaller multimers, and mixtures of assembled species. The direct observation of aggregates via unusual NMR spectra also correlated with promiscuous behavior of molecules in off-target in vitro pharmacology assays. This empirical assay can have utility for predicting compound promiscuity and should complement predictive methods that principally rely on the computing of descriptors such as lipophilicity (cLogP) and topological surface area (TPSA). This assay should serve as a practical tool for medicinal chemists to monitor compound attributes in aqueous solution and various pharmacologically relevant media, as demonstrated herein.

Predicting sorption of pharmaceuticals and personal care products onto soil and digested sludge using artificial neural networks

A comprehensive analytical investigation of the sorption behaviour of a large selection of over-the-counter, prescribed pharmaceuticals and illicit drugs to agricultural soils and freeze-dried digested sludges is presented. Batch sorption experiments were carried out to identify which compounds could potentially concentrate in soils as a result of biosolid enrichment. Analysis of aqueous samples was carried out directly using liquid chromatography-tandem mass spectrometry (LC-MS/MS). For solids analysis, combined pressurised liquid extraction and solid phase extraction methods were used prior to LC-MS/MS. Solid-water distribution coefficients (K(d)) were calculated based on slopes of sorption isotherms over a defined concentration range. Molecular descriptors such as log P, pK(a), molar refractivity, aromatic ratio, hydrophilic factor and topological surface area were collected for all solutes and, along with generated K(d) data, were incorporated as a training set within a developed artificial neural network to predict K(d) for all solutes within both sample types. Therefore, this work represents a novel approach using combined and cross-validated analytical and computational techniques to confidently study sorption modes within the environment. The logarithm plots of predicted versus experimentally determined K(d) are presented which showed excellent correlation (R(2) > 0.88), highlighting that artificial neural networks could be used as a predictive tool for this application. To evaluate the developed model, it was used to predict K(d) for meclofenamic acid, mefenamic acid, ibuprofen and furosemide and subsequently compared to experimentally determined values in soil. Ratios of experimental/predicted K(d) values were found to be 1.00, 1.00, 1.75 and 1.65, respectively.

Resveratrol analogues as selective cyclooxygenase-2 inhibitors: synthesis and structure-activity relationship.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is found in grapes and various medical plants. Among cytotoxic, antifungal, antibacterial cardioprotective activity resveratrol also demonstrates non-selective cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) inhibition. In order to find more selective COX-2 inhibitors a series of methoxylated and hydroxylated resveratrol derivatives were synthesized and evaluated for their ability to inhibit both enzymes using in vitro inhibition assays for COX-1 and COX-2 by measuring PGE(2) production. Hydroxylated but not methoxylated resveratrol derivatives showed a high rate of inhibition. The most potent resveratrol compounds were 3,3',4',5-tetra-trans-hydroxystilbene (COX-1: IC(50)=4.713, COX-2: IC(50)=0.0113 microM, selectivity index=417.08) and 3,3',4,4',5,5'-hexa-hydroxy-trans-stilbene (COX-1: IC(50)=0.748, COX-2: IC(50)=0.00104 microM, selectivity index=719.23). Their selectivity index was in part higher than celecoxib, a selective COX-2 inhibitor already established on the market (COX-1: IC(50)=19.026, COX-2: IC(50)=0.03482 microM, selectivity index=546.41). Effect of structural parameters on COX-2 inhibition was evaluated by quantitative structure-activity relationship (QSAR) analysis and a high correlation was found with the topological surface area TPSA (r=0.93). Docking studies on both COX-1 and COX-2 protein structures also revealed that hydroxylated but not methoxylated resveratrol analogues are able to bind to the previously identified binding sites of the enzymes. Hydroxylated resveratrol analogues therefore represent a novel class of highly selective COX-2 inhibitors and promising candidates for in vivo studies.