QSAR, QSPR and QSRR in Terms of 3‐D‐MoRSE Descriptors for In Silico Screening of Clofibric Acid Analogues

Abstract

A series of 27 analogues of clofibric acid, mostly heteroarylalkanoic derivatives, have been analyzed by a novel high-throughput reversed-phase HPLC method employing combined gradient of eluent's pH and organic modifier content. The such determined hydrophobicity (lipophilicity) parameters, log kw , and acidity constants, pKa , were subjected to multiple regression analysis to get a QSRR (Quantitative StructureRetention Relationships) and a QSPR (Quantitative Structure-Property Relationships) equation, respectively, describing these pharmacokinetics-determining physicochemical parameters in terms of the calculation chemistry derived structural descriptors. The previously determined in vitro log EC50 values - transactivation activity towards PPARα (human Peroxisome Proliferator-Activated Receptor α) - have also been described in a QSAR (Quantitative StructureActivity Relationships) equation in terms of the 3-D-MoRSE descriptors (3D-Molecule Representation of Structures based on Electron diffraction descriptors). The QSAR model derived can serve for an a priori prediction of bioactivity in vitro of any designed analogue, whereas the QSRR and the QSPR models can be used to evaluate lipophilicity and acidity, respectively, of the compounds, and hence to rational guide selection of structures of proper pharmacokinetics.

Lipophilicity study of fifteen fluoroquinolones by reversed-phase thin-layer chromatography

“…Therefore, other methods that are not susceptible to those problems have been developed for determination of lipophilicity. These include chromatographic methods, reversedphase thin layer chromatography (RP-TLC), [6][7][8][10][11][12][13][14][15][16] highperformance liquid chromatography on reversed-phase (RP-HPLC), 8,[17][18][19][20] and other indirect methods including micellar electrokinetic chromatography (MEKC), 9,21 and also the use of microemulsion (MEEKC) 9,22 and vesicles/liposomes (VEKC/ LEKC). 9,23 However, in recent years thin layer chromatography was most frequently used.…”

QSAR and docking studies on Triazole Benzene Sulfonamides with human Carbonic anhydrase IX inhibitory activity

“…The impact of different interatomic distances can be identified by dynamics of cumulative sum of 3D‐MoRSE terms ordered by interatomic distance. If increasing values of some 3D‐MoRSE descriptor lead to increase in biological activity, then atomic groups that contribute to the 3D‐MoRSE descriptor mostly are preferential for activity . 3D‐MoRSE descriptors interpretation can be done by estimating favorable optimal range MoRSE values needed for best activity and finding favorable interatomic distance in active compounds, which is compared with non‐actives.…”

Examination of lipophilicity and toxicity of azo dyes derivatives

“…Dokazano je da mnoge azo boje imaju kancerogeno [11,12], mutageno [13,14] Stoga je za mogućnost primene novosintetisanih azo boja neophodno usaglasiti njihove kvalitativne karakteristike, zahteve društva i ekološke propise [18]. U tom cilju se pre same sinteze novih derivata azo boja, identifikacija potencijalno biološki aktivnih među njima vrši primenom matematičkih modela koji omogućavaju uspostavljanje kvantitativnih zavisnosti između njihove strukture, fizičko-hemijskih svojstava i aktivnosti [19]. Među brojnim molekulskim deskriptorima koji mogu ukazati na potencijalnu bioaktivnost jedinjenja, lipofilnost zauzima najvažnije mesto.…”

“…U tom cilju se pre same sinteze novih derivata azo boja, identifikacija potencijalno biološki aktivnih među njima vrši primenom matematičkih modela koji omogućavaju uspostavljanje kvantitativnih zavisnosti između njihove strukture, fizičko-hemijskih svojstava i aktivnosti [19]. Među brojnim molekulskim deskriptorima koji mogu ukazati na potencijalnu bioaktivnost jedinjenja, lipofilnost zauzima najvažnije mesto.…”