Assessment of the pharmacokinetic profile of novel s-triazine derivatives and their potential use in treatment of Alzheimer's disease.
OBJECTIVE
The current treatment of Alzheimer's disease is purely symptomatic. Scientists are looking for new treatment options which could alter the course of the disease and improve the quality of life in patients with Alzheimer's disease. In this paper 14 novel s-triazine molecules have been evaluated for their lipophilicity. In addition docking study was carried out to evaluate acetylcholinesterase activity of these compounds.


METHODS
Lipophilicity was evaluated by RP HPTLC using 5 different mobile phases and obtained results were used in calculations of pharmacokinetic parameters - logBB, Ka and Pej. Multiple linear regression analysis was refined, taking account of molecular polarity (total polar surface area, TPSA) and molecular weight (Mw) descriptors. Appropriate QSAR models were developed. Docking studies were carried out using the Vina docking.


RESULTS
Five out of fourteen compounds evaluated [5-10] are selected as the most promising compounds with satisfactory pharmacokinetic properties and good docking scores.


CONCLUSIONS
Compound 10 possesses the best combination of favourable pharmacokinetic characteristics (brain penetration, intestinal absorption) and capacity for acetylcholinesterase inhibition. Consequently this molecule should be further evaluated for potential therapeutic use in Alzheimer's disease.
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia. Electronic address: jovanatrifunovic@gmx.com.
Jovana
J
Trifunović
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia.
Vladan
V
Borčić
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia.
Saša
S
Vukmirović
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Serbia.
Momir
M
Mikov
D000110:Acetylcholinesterase / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D012995:Solubility; D014227:Triazines / Q000737:chemistry* / Q000493:pharmacokinetics* / Q000494:pharmacology
D002800:Cholinesterase Inhibitors; D014227:Triazines; D000110:Acetylcholinesterase
Alzheimer's disease; Lipophilicity; Molecular docking; QSAR; s-Triazine