Naslov
QSAR Studies and Predicted Toxicity of N- Arylhydroxamic Acids

Autori
Jadrijević-Mladar Takač, Milena ; Barbarić, Monika

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Arhiv za higijenu rada i toksikologiju/Archives for Industrial Toxicology (Arh Hig Rada Toksikol, Vol. 67/Suppl. 1/pp. 1-80, Zagreb 2016 (ISSN 0004- 1254, UDC 613-6, CODEN AHRTAN) / Durgo, Ksenija ; Pavlaković, Željana ; Herman, Makso - Zagreb : Institute for Medical Research and Occupational Health, Zagreb, Hrvatska, 2016, 62-62

Skup
5th Croatian Congress of Toxicology with International Participation (CROTOX 2016)

Mjesto i datum
Poreč, Hrvatska, 09.10.2016. - 12.10.2016

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
QSAR ; N-arylhydroxamic acids ; molecular descriptors ; drug-likeness ; ADMET properties

Sažetak
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).

Izvorni jezik
Engleski

Znanstvena područja
Farmacija

POVEZANOST RADA