title: Synthesis, antimicrobial and anticonvulsant screening of small library of tetrahydro-2H-thiopyran-4-yl based thiazoles and selenazoles.
abstract: Synthesis and investigation of antimicrobial activity of 22 novel thiazoles and selenazoles derived from dihydro-2H-thiopyran-4(3H)-one are presented. Additionally, anticonvulsant activity of six derivatives is examinated. Among the derivatives, compounds 4a-f, 4i, 4k, 4 l, 4n, 4o-s and 4v have very strong activity against Candida spp. with MIC = 1.95-15.62 μg/ml. In the case of compounds 4a-f, 4i, 4k, 4 l, 4n, 4o, 4r and 4s, the activity is very strong against some strains of Candida spp. isolated from clinical materials, with MIC = 0.98 to 15.62 μg/ml. Additionally, compounds 4n-v are found to be active against Gram-positive bacteria with MIC = 7.81-62.5 μg/ml. The results of anticonvulsant screening reveal that compounds 4a, 4b, 4m and 4n demonstrate a statistically significant anticonvulsant activity in the pentylenetetrazole model, whereas compounds 4a and 4n showed protection in 6-Hz psychomotor seizure model. Noteworthy, none of these compounds impaired animals' motor skills in the rotarod test. We also performed quantum chemical calculation of interaction and binding energies in complex of 4a with cyclodextrin.
authors.affiliation: a Department of Chemical Technology and Pharmaceuticals , Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University , Bydgoszcz , Poland.
authors.forename: Krzysztof Z
authors.initials: KZ
authors.lastname: Łączkowski
authors.affiliation: b Department of Pharmaceutical Microbiology , Faculty of Pharmacy, Medical University , Lublin , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Biernasiuk
authors.affiliation: c Institute of Physics, Kazimierz Wielki University , Bydgoszcz , Poland , and.
authors.forename: Angelika
authors.initials: A
authors.lastname: Baranowska-Łączkowska
authors.affiliation: a Department of Chemical Technology and Pharmaceuticals , Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University , Bydgoszcz , Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Zielińska
authors.affiliation: d Chair of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Medical College , Krakow , Poland.
authors.forename: Kinga
authors.initials: K
authors.lastname: Sałat
authors.affiliation: d Chair of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University, Medical College , Krakow , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Furgała
authors.affiliation: a Department of Chemical Technology and Pharmaceuticals , Faculty of Pharmacy, Collegium Medicum, Nicolaus Copernicus University , Bydgoszcz , Poland.
authors.forename: Konrad
authors.initials: K
authors.lastname: Misiura
authors.affiliation: b Department of Pharmaceutical Microbiology , Faculty of Pharmacy, Medical University , Lublin , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Malm
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D016566:Organoselenium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012640:Seizures / Q000188:drug therapy; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D000935:Antifungal Agents; D016566:Organoselenium Compounds; D054852:Small Molecule Libraries; D013844:Thiazoles
keywords: Anticonvulsant activity; Candida spp.; selenazole; tetrahydro-4H-thiopyran-4-one; thiazole