title: A Physicochemical and Pharmacological Study of the Newly Synthesized Complex of Albendazole and the Polysaccharide Arabinogalactan from Larch Wood.
abstract: Inclusion complexes of albendazole (ABZ) with the polysaccharide arabinogalactan from larch wood Larix sibirica and Larix gmelinii were synthesized using a solid-state mechanochemical technology. We investigated physicochemical properties of the synthesized complexes in the solid state and in aqueous solutions as well as their anthelmintic activity against Trichinella spiralis, Hymenolepis nаna, Fasciola hepatica, Opisthorchis felineus, and mixed nematodoses of sheep. Formation of the complexes was demonstrated by means of intrinsic solubility and the NMR relaxation method. The mechanochemically synthesized complexes were more stable in comparison with the complex produced by mixing solutions of the components. The complexes of ABZ showed anthelmintic activity at 10-fold lower doses than did free ABZ. The complexes also showed lower acute toxicity and hepatotoxicity. These results suggest that it is possible to design new drugs on the basis of the ABZ:arabinogalactan complex that are safer and more effective than albendazole.
authors.affiliation: Institute of Solid State Chemistry and Mechanochemistry of Siberian Branch of Russian Academy of Sciences, Kutateladze, 18, Novosibirsk, 630128, Russia. j.chistyachenko@gmail.com.
authors.forename: Yulia S
authors.initials: YS
authors.lastname: Chistyachenko
authors.forename: Elizaveta S
authors.initials: ES
authors.lastname: Meteleva
authors.forename: Maria Y
authors.initials: MY
authors.lastname: Pakharukova
authors.forename: Aleksey V
authors.initials: AV
authors.lastname: Katokhin
authors.forename: Mikhail V
authors.initials: MV
authors.lastname: Khvostov
authors.forename: Anastasiya I
authors.initials: AI
authors.lastname: Varlamova
authors.forename: Igor I
authors.initials: II
authors.lastname: Glamazdin
authors.forename: Salavat S
authors.initials: SS
authors.lastname: Khalikov
authors.forename: Nikolay E
authors.initials: NE
authors.lastname: Polyakov
authors.forename: Ivan A
authors.initials: IA
authors.lastname: Arkhipov
authors.forename: Tatyana G
authors.initials: TG
authors.lastname: Tolstikova
authors.forename: Viatcheslav A
authors.initials: VA
authors.lastname: Mordvinov
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Dushkin
authors.forename: Nikolay Z
authors.initials: NZ
authors.lastname: Lyakhov
mesh_terms: D015766:Albendazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002627:Chemistry, Physical; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005210:Fasciola hepatica / Q000187:drug effects; D005685:Galactans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects; D048189:Hymenolepis nana / Q000187:drug effects; D028221:Larix / Q000737:chemistry*; D051379:Mice; D009348:Nematoda / Q000187:drug effects; D009891:Opisthorchis / Q000187:drug effects; D010316:Particle Size; D012756:Sheep; D012995:Solubility; D013329:Structure-Activity Relationship; D013499:Surface Properties; D017160:Trichinella spiralis / Q000187:drug effects; D014235:Trichinellosis / Q000188:drug therapy; D014934:Wood / Q000737:chemistry*
chemical_list: D005685:Galactans; D015766:Albendazole; C005653:arabinogalactan