Pharmacokinetics and tissue distribution of N-(2-hydroxyphenyl)-2-propylpentanamide in Wistar Rats and its binding properties to human serum albumin.
N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a novel valproic acid derivative that has shown anti-proliferative activity against epitheloid cervix carcinoma (HeLa), rhabdomyosarcoma (A204), and several breast cancer cell lines. The aim of this research was to evaluate the pharmacokinetic profile and tissue distribution of HO-AAVPA in Wistar rats, as well as its human serum albumin binding potential by experimental and in silico methods. A single dose of HO-AAVPA was given to male rats by intravenous, intragastric or intraperitoneal routes at doses of 25, 100, and 100 mg/kg, respectively. Then, blood samples were drawn at predetermined intervals of time, and the HO-AAVPA concentration in the plasma was quantified with a validated HPLC method. The elimination half-life (t1/2) was approximately 222 min, and the systemic clearance (CL) and apparent volume of distribution (Vd) were 2.20 mL/min/kg and 0.70 L/kg, respectively. The absolute oral bioavailability of HO-AAVPA was 33.8%, and the binding rate of HO-AAVPA with rat plasma proteins was between 66.2% and 83.0%. Additionally, in silico, UV and Raman spectroscopy data showed weak interactions between the test compound and human serum albumin. Thus, the results that were obtained demonstrated that despite its low oral bioavailability, the potential anticancer agent HO-AAVPA exhibits acceptable pharmacokinetic properties that would allow it to reach its site of action and exert its pharmacological effect in Wistar Rats, and it has a convenient profile for future assays to evaluate its human applications.
['Correa-Basurto|Ana María|AM|', 'Romero-Castro|Aurelio|A|', 'Correa-Basurto|José|J|', 'Hernández-Rodríguez|Maricarmen|M|', 'Soriano-Ursúa|Marvin Antonio|MA|', 'García-Machorro|Jazmin|J|', 'Tolentino-López|Luis Esteban|LE|', 'Rosales-Hernández|Martha Cecilia|MC|', 'Mendieta-Wejebe|Jessica Elena|JE|']
D000284:Administration, Oral D000577:Amides D000818:Animals D000970:Antineoplastic Agents D001665:Binding Sites D001682:Biological Availability D007274:Injections, Intraperitoneal D007275:Injections, Intravenous D008297:Male D062105:Molecular Docking Simulation D056004:Molecular Dynamics Simulation D010420:Pentanes D011485:Protein Binding D017208:Rats, Wistar D000075462:Serum Albumin, Human D014018:Tissue Distribution D014635:Valproic Acid
Pharmacokinetics Valproic acid derivative Antitumor Docking Protein binding