[Synthesis, chemical and toxicological study of a new benzimidazol derivative].
Hydatidosis is a cosmopolitan parasitic disease that remains a real public health problem in highly endemic countries. Surgery is the mainstay treatment, but with significant morbidity and mortality. In addition, contraindications for surgery emphasize the importance of developing effective medications. Currently, albendazole is the main anti-hydatid agent used worldwide. It has proven efficacy but limited bioavailability due to weak absorption. In order to improve the bioavailability of this molecule we synthesized an ester of albendazole, which exhibits a totally modified solubility compared with the princeps compound. This synthesis was achieved with an output of 75%. The structure of the synthetic product was established by IR spectrometry and by proton nuclear magnetic resonance. A careful toxicity study revealed that this product has little toxicity when administered intraperitoneally and orally in mice, with a lethal dose 50 of 2,500 mg/kg per os and 2,250 mg/kg intraperitoneally, values comparable to those of albendazole. This in vitro parasitological study demonstrated that the chemical changes introduced on the albendazole molecule had no effect on its antiparasitic activity.
Ansar
M
M
Laboratoire de chimie thérapeutique, faculté de médecine et de pharmacie, université Mohamed V-Souissi, BP 6203, Rabat Instituts, Rabat, Maroc. ansarmhammed@gmail.com
Zellou
A
A
Faouzi
M E A
ME
Zahidi
A
A
Serroukh
S
S
Lmimouni
B E
BE
Cherrah
Y
Y
Taoufik
J
J
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004443:Echinococcosis / Q000188:drug therapy* / Q000469:parasitology; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D051379:Mice
D000977:Antiparasitic Agents; D001562:Benzimidazoles; D007202:Indicators and Reagents