In vitro antitumor activity, ADME-Tox and 3D-QSAR of synthesized and selected natural styryl lactones.

Prostate cancer is a common cause of death in men and a novel treating methods should be developed. In order to find a new drug for prostate cancer, a series of novel conformationally constrained analogues of (+)-goniofufurone and 7-epi-(+)-goniofufurone, as well as the newly synthesized styryl lactones containing the cinnamic acid ester groups were evaluated for in vitro cytotoxicity against prostate cancer cell (PC-3). Furthermore, prediction of physicochemical characteristics and drugability as well as in silico ADME-Tox tests of investigated compounds were performed.

On the characterization of novel biologically active steroids: Selection of lipophilicity models of newly synthesized steroidal derivatives by classical and non-parametric ranking approaches.

In this paper, the guidelines for the interpretation of the results of quantitative structure-retention relationship (QSRR) modeling, comparison and assessment of the established models, as well as the selection of the best and most consistent QSRR model were presented. Various linear and non-linear chemometric regression techniques were used to build QSRR models for chromatographic lipophilicity prediction of a series of triazole, tetrazole, toluenesulfonylhydrazide, nitrile, dinitrile and dione steroid derivatives. Linear regression (LR) and multiple linear regression (MLR) were used as linear techniques, while artificial neural networks (ANNs) were applied as non-linear modeling techniques.

A comparative study of chromatographic behavior and lipophilicity of selected natural styryl lactones, their derivatives and analogues.

This study is based on the analyses of the retention behavior of selected natural styryl lactones and their synthetic analogues in reversed-phase high-performance liquid chromatography. Chromatographic separations were achieved applying ZORBAX SB-C18 column and two different mobile phases: methanol-water and acetonitrile-water. Chromatographic lipophilicity of the analyzed compounds was defined by logk constant and correlated with in silico molecular descriptors.

Chemometrics approach based on chromatographic behavior, in silico characterization and molecular docking study of steroid analogs with biomedical importance.

Physicochemical characterization of steroid analogs (triazole, tetrazole, toluenesulfonylhydrazide, nitrile, dinitrile and dione) is considered to be a very important step in further drug selection. This study applies to the determination of lipophilicity of previously synthesized steroid derivatives using reversed-phase high-performance liquid chromatography (RP HPLC). Chemometric aspect of chromatographic lipophilicity is given throughout multiple linear regression (MLR) quantitative structure-retention relationships (QSRR) approach.

Lipophilicity estimation and characterization of selected steroid derivatives of biomedical importance applying RP HPLC.

The present paper deals with chromatographic lipophilicity determination of twenty-nine selected steroid derivatives using reversed-phase high-performance liquid chromatography (RP HPLC) combined with two mobile phase, acetonitrile-water and methanol-water. Chromatographic behavior of four groups (triazole and tetrazole, toluenesulfonylhydrazide, nitrile and dinitrile and dione) of selected steroid derivatives was studied. Investigated compounds were grouped using principal component analysis (PCA) according to their logk values for both mobile phases.

Preselection of A- and B- modified d-homo lactone and d-seco androstane derivatives as potent compounds with antiproliferative activity against breast and prostate cancer cells - QSAR approach and molecular docking analysis.

The problem with trial-and-error approach in organic synthesis of targeted anticancer compounds can be successfully avoided by computational modeling of molecules, docking studies and chemometric tools. It has been proven that A- and B- modified d-homo lactone and d-seco androstane derivatives are compounds with significant antiproliferative activity against estrogen-independent breast adenocarcinoma (ER-, MDA-MB-231) and androgen-independent prostate cancer cells (AR-, PC-3). This paper presents the quantitative structure-activity relationship (QSAR) models based on artificial neural networks (ANNs) which are able to predict whether d-homo lactone and/or d-seco androstane-based compounds will express antiproliferative activity against breast cancer cells (MDA-MB-231) or not.

Comprehensive QSRR modeling as a starting point in characterization and further development of anticancer drugs based on 17α-picolyl and 17(E)-picolinylidene androstane structures.

The selection of the most promising anticancer compounds from the pool of the huge number of synthesized molecules is a quite complex task. There are many compounds characterization approaches which can suggest the best structural features of a molecule with the highest antiproliferative effect on the certain type of cancer cell lines. One of these approaches is the lipophilicity determination of compounds and the analysis of its correlation with the anticancer activity.

RP-HPTLC Retention Data in Correlation with the In-silico ADME Properties of a Series of s-triazine Derivatives.

The properties relevant to pharmacokinetics and pharmacodynamics of four series of synthesized s-triazine derivatives have been studied by Quantitative structure-retention relationship (QSRR) approach. The chromatographic behavior of these compounds was investigated by using reversed-phase high performance thin-layer chromatography (RP-HPTLC). Chromatographic retention (R M (0)) was correlated with selected physicochemical parameters relevant to pharmacokinetics, i.

Prediction of In-silico ADME Properties of 1,2-O-Isopropylidene Aldohexose Derivatives.

Retention behaviour of molecules mostly depends on their chemical structure. Retention data of biologically active molecules could be an indirect relationship between their structure and biological or pharmacological activity, since the molecular structure affects their behaviour in all pharmacokinetic stages. In the present paper, retention parameters (R M (0)) of biologically active 1,2-O-isopropylidene aldohexose derivatives, obtained by normal-phase thin-layer chromatography (NP TLC), were correlated with selected physicochemical properties relevant to pharmacokinetics, i.

Non-linear assessment of anticancer activity of 17-picolyl and 17-picolinylidene androstane derivatives--chemometric guidelines for further syntheses.

The present paper deals with prediction of cytotoxic activity of 17-picolyl and 17-picolinylidene androstane derivatives toward androgen receptor negative prostate cancer cell line (PC-3). The prediction was achieved applying artificial neural networks (ANNs) method on the basis of molecular descriptors. The most important descriptors (skin permeability (SP), Madin-Darby canine kidney cell permeability (MDCK) and universal salt solubility factor (S+SF)) were selected by using stepwise selection coupled with partial least squares method.

Multivariate regression modelling of antifungal activity of some benzoxazole and oxazolo[4,5-b]pyridine derivatives.

In the present study, principal component analysis (PCA) followed by principal component regression (PCR) and partial least squares (PLS) method was applied in order to identify the most important in silico molecular descriptors and quantify their influence on antifungal activity (expressed as minimal inhibitory concentration) of selected benzoxazole and oxazolo[4,5-b]pyridine derivatives against Candida albicans. PLS regression showed the best statistical performance, according to the lowest value of the standard error (root mean square errors of calibration of 0.02526 and cross-validation of 0.

QSRR modeling of retention behavior of some s-triazine derivatives.

The properties relevant to lipophilicity of four series of synthesized s-triazine derivatives have been studied by quantitative structure-retention relationship (QSRR) approach. Examination of chromatographic behavior revealed a linear correlation between RM values and the volume fraction of mobile phase modifier. Furthermore, a reliable relationship was defined between the retention constants, RM0, and theoretically calculated bioactivity descriptors for lipophilicity and solubility.

Quantitative structure-retention relationship analysis of some xylofuranose derivatives by linear multivariate method.

The relationship between retention behavior of eight 1,2-O-cyclohexylidene xylofuranose derivatives and their molecular characteristics was studied using chemometric Quantitative Structure-Retention Relationships (QSRR) approach. QSRR analysis was carried out on the retention parameter RM0, obtained by normal-phase thin-layer chromatography, by using molecular descriptors, as well as partition coefficient for n-octanol/water bi-phase system (logP). Molecular descriptors were calculated from the optimized structures.

Quantitative structure-activity relationship (QSAR) study of a series of benzimidazole derivatives as inhibitors of Saccharomyces cerevisiae.

A quantitative structure activity relationship (QSAR) has been carried out on a series of benzimidazole derivatives to identify the structural requirements for their inhibitory activity against yeast Saccharomyces cerevisiae. A multiple linear regression (MLR) procedure was used to model the relationships between various physicochemical, steric, electronic, and structural molecular descriptors and antifungal activity of benzimidazole derivatives. The QSAR expressions were generated using a training set of 16 compounds and the predictive ability of the resulting models was evaluated against a test set of 8 compounds.