1,721,138 research outputs found
Hydrophobic Properties of Chromones and Flavones. Relationships Between Octanol/Water Partition Coefficients and RP‐HPLC Capacity Factors
No full textThe octanol/water partition coefficient (P) and the RP‐HPLC capacity factors (k′) at four different concentrations of organic modifier (methanol) in the mobile phase have been measured. The observed log P values of the polar substituted compounds show good consistency, if the interactions among the polar groups are taken into account on the basis of the Leo‐Fujita theory. Log P and log k′ are linearly correlated at the four methanol concentrations examined and at the extrapolated 0% methanol concentration. The phenolic compounds deviate from the correlation and this is recognized as a characteristic behaviour of the C‐18/ MeOH‐H2O chromatographic system. Copyright © 1987 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinhei
Comparative molecular field analysis of non-steroidal aromatase inhibitors related to fadrozole
No full textA series of non-steroidal inhibitors of aromatase, structurally related to fadrozole (2) , was investigated with the aim of developing a 3D QSAR model using the Comparative Molecular Field Analysis (CoMFA) technique. The alignment of the molecules was performed following two approaches (atomby-atom and field fit) , both starting from an initial hypothesis of superimposition of fadrozole to a steroidal inhibitor (3) . From a number of CoMFA models built with different characteristics, one was recognized as the most statistically relevant; this one is discussed in detail. The features of the 3D QSAR model are consistent with those of other 3D and QSAR models of aromatase and its inhibitors. © 1996 ESCOM Science Publishers B.V
Partition and distribution coefficients of aryloxypropanolamine β-adrenoceptor antagonists
No full textAbstract
n-Octanol/water partition and distribution coefficients of fifteen β-blockers have been measured and the relationships between log P (neutral species), log Pi (fully ionized species) and log D7·4 have been examined. A strict correlation exists among these three parameters, suggesting that the ionization exerts similar effects on the partition behaviour of these drugs.</jats:p
Looking for selectivity among cytochrome P450s inhibitors
No full textCytochrome P450s 19 and 17 are very important pharmacological targets in two different fields of cancer chemotherapy. We present here a theoretical study aimed at explaining the molecular basis of inhibitor affinity and selectivity for either P450 19 or P450 17. Docking simulations of two compounds pointed out the major physicochemical features associated with inhibitory activity. Our results, in agreement with site-directed mutagenesis experiments, could be of relevant utility when designing new P450 19 and P450 17 inhibitors
Acetylcholinesterase inhibitors in the context of therapeutic strategies to combat alzheimer's disease
No full textAcetylcholinesterase inhibitors (AChEIs) are a class of drugs useful in the treatment of Alzheimer's disease (AD) as a result of their indirect cholinomimetic effect. In this review, patents claiming AChEIs that have appeared from the late 1990s (after the marketing of second generation compounds) to the present day will be discussed. The patents filed in this period fall into two categories of AChEIs, new products and combinations of drugs. Most of the new compounds are modifications of known drugs, although some novel structures have been claimed. The association of AChEIs with other pharmacological agents is hoped to improve efficacy of treatment by combining effects from the different pharmacological mechanisms of action. To put this discussion of AChEIs into perspective, some observations on the clinical uses of the anticholinesterases are also briefly summarised
COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19
Full text linkThe COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet (http://compmedchem.unibo.it/covidrugnet), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection. Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies
In silico antitarget screening
No full textThe need to early predict the possible failure of a drug candidate is becoming an absolute requirement in the drug discovery process. For this reason, fromthe initial phases of lead development, great attention is paid to the ADMET characteristics of the compounds. In this context, the recent discovery that hitting some well identified macromolecular targets can induce undesired side effects has led drug designers to apply some classical in silico technologies to the goal of avoiding the interaction of lead candidates with such antitargets
A comparative study on the application of hierarchical-agglomerative clustering approaches to organize outputs of reiterated docking runs
No full textReiterated runs of standard docking protocols usually provide a collection of possible binding modes rather than pinpoint a single solution. Usually, this ensemble is then ranked by means of an energy-based scoring function. However, since many degrees of approximation have to be introduced in the computation of the binding free energy, scoring functions cannot always rank the experimental pose among the top scorers. Cluster analysis might help to overcome this limit, provided that data clusterability has been earlier assessed. In this paper, first, we present a modified version of a test earlier developed by Hopkins to assess whether or not docking outputs show the natural tendency to be grouped in clusters. Then, we report the results of a comparative study on the application of different hierarchical-agglomerative cluster rules to partition docking outputs. The rule that was able to best manage the observed data was finally applied to the whole ensemble of poses collected from several docking tools. The combination of the average linkage rule with the cutting function developed by Sutcliffe and co-workers turned out to be an approach that meets all of the criteria required for a robust clustering protocol. Furthermore, a consensus clustering allowed us to identify the pose closest to the experimental one within a statistically significant cluster, whose number was always of few units
A comparative QSAR analysis of acetylcholinesterase inhibitors currently studied for the treatment of Alzheimer's disease
No full textConsidering the relevance of acetylcholinesterase inhibitors as potential agents for the treatment of the Alzheimer's disease, we have undertaken a comparative QSAR analysis aimed at individuating the physico-chemical properties governing the inhibitory activity of such compounds. The QSAR equations for 13 series of derivatives have been calculated and discussed. The series studied are all those we found in the literature suitable for a QSAR analysis and represent the three main classes of acetylcholinesterase inhibitors currently investigated, namely, physostigmine analogues, 1,2,3,4-tetrahydroacridines and benzylamines. The equations we obtained show that, within each class, the main physico-chemical properties affecting the inhibitory activity are almost the same for all the series and can be individuated by the use of proper parameters. The conclusions of this study can be summarized as follows: (a) hydrophobicity plays a critical role in both the physostigmine-and the benzylamine-derived classes; (b) electronic effects are important for the interactions carried out by the variable portion of benzylamine derivatives; and (c) steric factors are also significant, but, as in other cases, the collinearity between steric and hydrophobic parameters does not allow one to draw any final conclusion
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