Biomaterial Database

Praziquantel meets Niclosamide: A dual-drug Antiparasitic Cocrystal. 2023

Ilenia D'Abbrunzo, and Emma Bianco, and Lara Gigli, and Nicola Demitri, and Rebecca Birolo, and Michele R Chierotti, and Irena Škorić, and Jennifer Keiser, and Cécile Häberli, and Dario Voinovich, and Dritan Hasa, and Beatrice Perissutti

Department of Chemical and Pharmaceutical Sciences, University of Trieste, P.le Europa 1, 34127 Trieste, Italy. Electronic address: s244105@ds.units.it.

In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P21/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.

UI	MeSH Term	Description	Entries
D009534	Niclosamide	An antihelmintic that is active against most tapeworms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p48)	Bayer 2353,Bayer 73,Bayluscide,Clonitralide,Fenasal,Niclocide,Niclosamide, 2-Aminoethanol (1:1),Phenasal,Radewerm,Trédémine,Yomesan
D011223	Praziquantel	An anthelmintic used in most schistosome and many cestode infestations.	Biltricide,Cesol,Cisticid,Cysticide,Droncit,Drontsit,EMBAY 8440,Prasiquantel,Praziquantel, (+-)-Isomer,Praziquantel, (R)-Isomer,Praziquantel, (S)-Isomer,Pyquiton,Traziquantel
D004364	Pharmaceutical Preparations	Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form.	Drug,Drugs,Pharmaceutical,Pharmaceutical Preparation,Pharmaceutical Product,Pharmaceutic Preparations,Pharmaceutical Products,Pharmaceuticals,Preparations, Pharmaceutical,Preparation, Pharmaceutical,Preparations, Pharmaceutic,Product, Pharmaceutical,Products, Pharmaceutical
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000871	Anthelmintics	Agents that kill parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.	Anthelmintic,Antihelmintic,Vermifuge,Vermifuges,Antihelmintics
D000977	Antiparasitic Agents	Drugs used to treat or prevent parasitic infections.	Antiparasitic,Antiparasitic Agent,Antiparasitic Drug,Parasiticide,Parasiticides,Antiparasitic Drugs,Antiparasitics,Agent, Antiparasitic,Agents, Antiparasitic,Drug, Antiparasitic,Drugs, Antiparasitic
D012550	Schistosoma mansoni	A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis.	Schistosoma mansonus,mansonus, Schistosoma
D017550	Spectroscopy, Fourier Transform Infrared	A spectroscopic technique in which a range of wavelengths is presented simultaneously with an interferometer and the spectrum is mathematically derived from the pattern thus obtained.	FTIR,Fourier Transform Infrared Spectroscopy,Spectroscopy, Infrared, Fourier Transform
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus