In Silico Taste–Toxicity Study of New Hypothetical Hetero-Abiraterone Derivatives

Abstract

First Iraqi attempt to study drug used for prostate cancer treatment (Abiraterone) that hypothetically reacted with known chemicals classified as Anticancer drug: Tirapazamine (T) and 5-Fluorouracil (F), food additive and preservative: Butylated Hydroxy Toluene (B) and Ethoxyquin (E), and sweeteners: P-4000 (P), Sodium Cyclamate (CS), Alitame (AT), and Saccharin (SA). The second step in this work was computational study of all reactants and the formed products having newly ether, amine, and carboxylic acid ester, and sulphonate bonds by online websites. Taste, toxicity, and ADMET were calculated by three online websites related to Charite University of Medicine, Institute for Physiology, Germany and University of Melbourne, Australia. SMILES of the reactants were obtained from National Library of Medicine/ National Center for Biotechnology Information websites while products were drawn by the molecular editor CS ChemDraw Ultra and rechecked by MarvinSketch program. This in Silico study showed various results of the formed products compared to Abiraterone (A) that predicated it as sour chemical belongs to Class 4 as a harmful substance if swallowed. Abiraterone (A) toxicity on liver organ was 61% probability percentage as hepatotoxicity while carcinogenicity, Immunotoxicity, Mutagenicity, cytotoxicity, AhR, AR, Aromatase, ER, HSE, and p53 were more than 70 % to bind Progesterone or Androgen. Also, Abiraterone (A) has a poor water solubility leading to high intestinal absorption, moderate total clearance, and giving inhibition reaction to Cytochrome P450 type CYP2C19, hERG II, and Ames test. These results confirmed that Abiraterone is structurally less harmful acute class with highly chance to interact with cell components resulting lethal response. All Abiraterone hypothetical products had a harmful reaction if swelled (Class 4), sour taste. All toxicological characters may be highly affected by its water solubility and intestinal absorption towards CNS, BBB, and CaCO₂ permeability, skin sensation, and Ames test issues. For example, this in Silico- QSAR foundations about Abiraterone – Saccharin (A-SA) suggest that A-SA is structurally safe and there are several possibilities of becoming an active–multiple toxicological compound.