Computer-aided prediction for medicinal chemistry via the Internet

Abstract

Some computational tools for medicinal chemistry freely available on the Internet were compared to examine whether the results of prediction obtained with different methods coincided or not. It was shown that the correlation coefficients varied from 0.65 to 0.90 for log P (seven methods), from 0.01 to 0.73 for aqueous solubility (four methods), and from 0.19 to 0.73 for drug-likeness (three methods). While for log P estimates, reasonable average pairwise correlation was found, for aqueous solubility and drug-likeness it was rather poor. Therefore, using computational tools freely available via the Internet, medicinal chemists should evaluate their accuracy versus experimental data for particular series of compounds. In contrast to prediction of above mentioned properties, which can be done with several Internet tools, wide profiling of biological activity can be obtained only with PASS Inet (http://www.ibmc.msk.ru/PASS). PASS Inet was tested by a dozen medicinal chemists for compounds from different chemical series with various kinds of biological activity, and in the majority of cases the results of prediction coincided with the experiments. New anxiolytics, antiarrhythmics, antileishmanials, and other biologically active agents have been identified on this basis. The advantages and limitations of computer-aided predictions for medicinal chemistry via the Internet are discussed.

Normal and reversed phase thin layer chromatography data in quantitative structure–activity relationship study of compounds with affinity for serotonin (5-HT) receptors

“…In the case of binding affinity (pK i ) to the receptor, both for NP and RP2 TLC system, the relationships demonstrated values of the determination coefficient below 49% (Eqs. (3) and (4)). For compounds with agonistic activity pD 2 , the correlations explain 59-67% of the total variance (Eqs.…”

“…Experimental determination of such activity is a time-consuming and costly process, based on the knowledge and experience of highly qualified experts (biologists, pharmacologists). Computer-aided methods, allowing to predict in parallel even over ten types of biological activity of novel, potentially therapeutic compounds, are used in this field in addition to standard biological tests [1][2][3][4]. Such methods are based mainly on analysis of the structure-activity correlations and comparisons with the database, consisting of substances with known biological activity.…”

“…So far, seven families of such receptors (5-HT 1 -5-HT 7 ) were distinguished and several subtypes within each family. They are all classified as metabotropic receptors, except for the 5-HT 3 family, which belongs to the ionotropic receptor class [23]. As established on the basis of literature data, the following amino acids play an essential role in formation of drug-serotonin (5-HT) receptor complex: aspartic acid (Asp155), serine (Ser159), phenylalanine (Phe340), asparagine (Asn333), tryptophan (Trp200, 236, 367), tyrosine (Tyr370) and threonine (Thr196) [12][13][14][15][16][17][18][19][20][21][22].…”

Regioselective acylation of congeners of 3-amino-1H-pyrazolo[3,4-b]quinolines, their activity on bacterial serine/threonine protein kinases and in vitro antibacterial (including antimycobacterial) activity

“…Since there is no information to provide reliable SAR that could be a basis for the directed synthesis of 3-amino-1H-pyrazolo [3,4-b]quinolines BSTK inhibitors, we implemented virtual screening by PASS-online 15 . This Internet resource provides probability of wide ranging pharmacological activities for individual compounds.…”

“…This Internet resource provides probability of wide ranging pharmacological activities for individual compounds. Software PASS-online are based on probabilistic methodology of experimental activity for chemical fragments 15 .…”