化合物脂水分配系数计算软件及比较研究

目的:介绍几种常用的化合物脂水分配系数计算软件,并比较它们的准确度和适用范围等。方法:从分子结构出发,运用CLOGP、ACD/LogP、Pallas和Molinspiration 4种计算软件获得logP值,比较其计算准确度。结果:本文选择的4种计算软件均能比较准确的计算出化合物的logP值。结论:运用软件计算的方法得到大批量化合物的logP值,有助于计算机辅助药物设计。

In silico assessment of human health risks caused by cyanotoxins from cyanobacteria

Harmful algal blooms(HABs)that are formed by cyanobacteria have become a serious issue worldwide in recent years.Cyanobacteria can release a type of secondary metabolites called cyanotoxins into aquatic systems which may indirectly or directly provide health risks to the environment and humans.Cyanotoxins provide some of the most powerful natural poisons including potent neurotoxins,hepatotoxins,cytotoxins,and endotoxins that may result in environmental health risks,and long-term morbidity and mortality to animals and humans.In this research,we used the chemcomputational tool Molinspiration for molecular property predictions,Pred-hERG 4.2 web software for cardiac toxicity prediction,and Pred-Skin 2.0 web software for predicting skin sensitization.We are predicting some toxicological aspects of cyanobacteria here using chemcomputational tools with the hypothesis that cyanotoxins are providing a risk to human health.We are using the tool Pred-hERG 4.2 to predict hERG channel blocking potential and the Pred-skin tool to predict skin sensitization due to cyanotoxins.The potential of anatoxin,ambigol,the microcystin group,and lyngbyatoxin A,lyngbyatoxin B,nodularin-R,and saxitoxin were predicted to cause skin sensitization in the final results(consensus model).Anatoxin-a and lyngbyatoxin were predicted to allow GI absorption and blood–brain barrier penetration.Among the 20 predicted cyanotoxins only aeruginosin 103-A,ambigol A,and ambigol were predicted by Pred-hERG 4.2 according to the applicability domain results as potential cardiotoxins with weak or moderate potency.Lyngbyatoxin shows activity through the GPCR ligand and protease,kinase,and enzyme inhibitor.

Computational Calculations of Molecular Properties and Molecular Docking of New and Reference Cephalosporins on Penicillin Binding Proteins and Various β-Lactamases

An approach of using molinspiration calculations and molecular docking on PBPs （penicillin-binding proteins） and certain β-lactamases is employed to predict the molecular properties, bioactivity and resistance of newer and reference cephalosporins. The previously synthesized cephalosporins 1-8 and reference cephalosporins were subjected to extensive evaluations by calculating the molecular properties, drug-likeness scores on the bases of Lipinski＇s rule and bioactivity prediction using the method of molinspiration web-based software. The TPSA （topological polar surface area）, OH-NH interactions, n-violation and the molinspiration Log partition coefficient （miLogP） values were also calculated. The investigated cephalosporins were subjected to molecular docking study on PBPs （lpyy） and on β-lactamases produced by S. aureus, K. pneumonia, E. coil and P. auroginosa using 1-click-docking website. Molecular properties of 1-8 recorded higher ＂FPSA than cephalexin and were lower than the reference cephalosporins and do not fulfill the requirements for Lipinski＇s rule. Bioactivities of 1-8 were predicted to be less and their docking scores on PBPs were comparable to those of the reference cephalosporins, particularly ceftobiprole. The references recorded various docking scores on the above β-lactamases and as expected, cefiobiprole recorded the lowest scores on all β-lactarnases. Cephalosporins 1-8 recorded various docking scores on β-lactamases. Molecular docking studies on PBPs and β-lactamases are considered as very useful, reliable and practical approach for predicting the bioactivity scores and to afford some information about the stability and selectivity of the newly proposed cephalosporins against β-lactamases of certain pathogenic microbes, such as P. auroginosa and MRSA, by recording the relative docking scores in comparison with those of reference cephalosporins.