Evaluation of log Po/w values of drugs from some molecular structure calculation softwares

Abstract

Predictive software packages to estimate the lipophilicity of molecules have become key tools in the new drug design. Six different well-known computational programs including the classical BioByte-clogP and the GALAS algorithm offered by ACDlabs were evaluated through a set of 103 drugs with different structures and functionalities. To evaluate the predictions accuracy, reliable experimental log P o/w values for the whole testing set were carefully selected. The best estimations are performed by GALAS/logP based on the fragmental method, corrected according to the similarity with compounds included in the software training set.

Synthesis, spectral analysis and in vitro cytotoxicity of diorganotin (IV) complexes derived from indole‐3‐butyric hydrazide

“…4,7,11,15,16,19 and 20 compounds does not show the lipophilic nature (log P) due to its value is F I G U R E 3 Graph showing antimicrobial activity of the synthesized compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) more than 5 value. [64] The TPSA value of compounds was less than 130 Å 2 which shows good transport properties of compounds. The percentage absorption of the compounds was calculated by using the formula % Abs = 109-(0.345 × TPSA).…”

Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

“…Prediction software can be very useful and convenient for a preliminary and rapid estimate of the lipophilicity of potential drug candidates. In general terms and for the most commonly used programs, the lipophilicity of the whole molecule is calculated from the individual contributions of separate atoms and/or structural fragments, and in some cases from intramolecular interactions [2,3]. In combination with calculated pK a values, such software provides a rough estimate of lipophilicity profiles (log D o/w vs. pH), which is very useful as a starting point in experimental designs of accurate log P o/w determination.…”

Setup and validation of shake-flask procedures for the determination of partition coefficients (logD) from low drug amounts

“…The partition coefficient (P) refers to the ratio of compound concentration in each phase and can be determined experimentally by a variety of methods including the well-known shake-flask method (EPA, 1996;OECD 107 Method, 1995), potentiometric methods (Avdeef, 1993(Avdeef, , 1992Ràfols et al, 2012;Takács-Novák and Avdeef, 1996), chromatographic methods (Donovan and Pescatore, 2002;Kaliszan et al, 2002;Liang and Lian, 2015;OECD 117 Method, 2004;Pallicer et al, 2012Pallicer et al, , 2010Wiczling et al, 2008) and others. Besides, lipophilicity can also be estimated using computer software and extensive studies about the accuracy of calculated log P values by different computer software has already been carried out (Chou and Jurs, 1979;Leo, 1987;Mannhold et al, 2009;Pallicer et al, 2014;Tetko et al, 2009). However, when an ionizable compound is equilibrated in a two-phase system at a pH at which it is partially ionized, its concentration in the organic and aqueous phases is directly related to the distribution coefficient (D), which is defined as the ratio of the concentrations of both the ionized and unionized species of the compound in the organic and aqueous phases at a determined pH value (Scherrer and Howard, 1977).…”