Naslov
Retinoic Acid Activity on Mamalian Embryo in Organ Culture and Evaluation of Hazard and Risk in Correlation Studies between Molecular Descriptors and ADMET Parameters in a Series od X-Category Drugs

Autori
Jadrijević-Mladar Takač, Milena ; Crnek-Kunstelj, Vesna ; Barbarić, Monika ; Takač, Vedran

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

Izvornik
Abstracts, 5th PSWC, Poster Session Online, Virtual Gallery / Joseph T. DiPiro - Hag : International Pharmaceutical Federation (FIP), 2014, PC-006

Skup
5th FIP Pharmaceutical Sciences World Congress (PSWC), Pharmaceutical Sciences beyond 2020 – The Rise of a New Era in Healthcare

Mjesto i datum
Melbourne, Australija, 13.04.2014. - 16.04.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Embryo-derived teratomas; Retinoic acid; Retinouds; X-Category drugs; ADMET; Molecular descriptors; Drug-likeness; Toxicity; QSAR

Sažetak
The results of our previous work on mammalian embryo-derived teratomas in organ culture treated with either retinoic acid (RA, c = 10-5 mol/L) or neural growth factor (NGF, 100 ng/mL) showed no influence on neural tissue differentiation. On the contrary the combination of RA and NGF influenced neural tissue differentiation (100%) and inhibition of other tissues (epidermis, gland epithelium, cartilage). The influence of RA, either alone or in presence of NGF on potential teratogenicity has been revealed in this model. In continuation of this work we have explored the molecular features of retinoids in a series of selected X-category drugs in correlation studies between computed molecular descriptors (MDs) and ADMET parameters. Computed MDs and ADMET parameters of 37 drug molecules were predicted by MedChem ADMET Predictor Module (Simulations Plus. Inc. USA). All correlation analyses were performed using OriginPro 8.0 software (Origin Laboratories, USA). Most investigated molecules were amides or lactams with the possibility of biotransformation to corresponding acids. Interesting relationships were obtained in correlations of computed lipophilicity (MLog P) and total polar surface area (TPSA) with hERG toxicity (TOX hERG), i.e. MLogP v.s TOX hERG (y = 0.619x + 3.918, r = 0.977), and TPSA v.s. hERG (y =-0.016x + 7.024, r = 0.912). In both correlations, a two sets of molecules were observed, one with high collinear relationship between TOX hERG with either MLogP or TPSA, while the other set was a cluster of diverse X-category drugs. For all retinoids included in this study, the ADMET Risk of 4, TOX Risk of 2, while TOX MUT Risk of 1 for retinol and etretinate, were predicted.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Farmacija

POVEZANOST RADA