QSAR Studies and Predicted Toxicity of N- Arylhydroxamic Acids (CROSBI ID 642284)
Prilog sa skupa u časopisu | sažetak izlaganja sa skupa | međunarodna recenzija
Podaci o odgovornosti
Jadrijević-Mladar Takač, Milena ; Barbarić, Monika
engleski
QSAR Studies and Predicted Toxicity of N- Arylhydroxamic Acids
The use of biological property predictions has increased in recent years due to improvements in computer technology, the rising costs of drug discovery, and a desire by regulatory agencies to better understand, predict and improve drug safety. Recently, compounds with hydroxamic moiety, i.e., hydroxamic acids (R1CON(OH)R2, R1 = alkyl/aryl and R2 = alkyl/aryl or H) have attracted researchers interest since they show a wide range of biological activities and acceptable toxicities. The aim of this study was to investigate N-arylhydroxamic acids in order to explore their biological activity and potential toxicity in relation to their chemical structures. For this purpose different molecular descriptors including topological indices (MDs, i.e. natoms, Mr, V, MlogP and TIs), drug-likeness (DLs, i.e., GPCR ligand (GPCR l), ion channel modulator (ICM), kinase inhibitor (KI), nuclear receptor ligand (NRL), protease inhibitor (PI) and enzyme inhibitor (EI) and ADMET parameters in comparison with vorinostat* /ADMET Risk (1 – 5.272 ; 3.197*), CYP Risk (0 – 1.055 ; 0.697*), TOX Risk (1 – 2 ; 2*), TOX MUT Risk (1 – 4 ; 2*), TOX hERG Risk (4.541 – 5.579 ; 4.855*)/ have been computed. The relationship between chemical structure either with antitumor activity or predicted toxicity of investigated compounds were analyzed by QSAR methods. Metabolic pathways of N-arylhydroxamic acids with CYP enzymes have been also predicted by ADMET PredictorTM 8.0 (Simulations Plus Inc., USA) and analyzed. Obtained results suggest that some of the investigated N-arylhydroxamic acids are with better toxicological profile comparing to hydroxamic acids registered for clinical use as antitumor agents (e.g., vorinostat and belinostat).
QSAR ; N-arylhydroxamic acids ; molecular descriptors ; drug-likeness ; ADMET properties
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Podaci o prilogu
62-62.
2016.
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objavljeno
Podaci o matičnoj publikaciji
Arhiv za higijenu rada i toksikologiju
Durgo, Ksenija ; Pavlaković, Željana ; Herman, Makso
Zagreb: Institute for Medical Research and Occupational Health, Zagreb, Hrvatska
0004-1254
1848-6312
Podaci o skupu
5th Croatian Congress of Toxicology with International Participation CROTOX 2016
poster
09.10.2016-12.10.2016
Poreč, Hrvatska