molecules Article Synthesis and Antifungal Screening of 2-{[1-(5-Alkyl/arylalkylpyrazin-2- yl)ethylidene]hydrazono}-1,3-thiazolidin-4-ones † Veronika Opletalova 1 , Jan Dolezel 2 , Jiri Kunes 3 , Vladimir Buchta 4,5 , Marcela Vejsova 4,5 and Marta Kucerova-Chlupacova 1, * 1 Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; opletalova@faf.cuni.cz 2 GlaxoSmithKline, Hvezdova 1734/2c, 140 00 Prague, Czech Republic; jan.j.dolezel@gsk.com 3 Department of Inorganic and Organic Chemistry, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; kunes@faf.cuni.cz 4 Department of Biological and Medical Sciences, Faculty of Pharmacy in Hradec Kralove, Charles University, Heyrovskeho 1203, 500 05 Hradec Kralove, Czech Republic; buchta@faf.cuni.cz (V.B.); vejsova@faf.cuni.cz (M.V.) 5 Department of Clinical Microbiology, University Hospital Hradec Kralove, Sokolska 581, 500 05 Hradec Kralove, Czech Republic * Correspondence: kucerom@faf.cuni.cz; Tel.: +420-495-067-373 † Preliminary Results Were Presented at the 8th Central European Conference “Chemistry towards Biology” (CTB-2016), Brno, Czech Republic, 28 August–1 September 2016 (Poster P-56). Academic Editor: Derek J. McPhee Received: 30 September 2016; Accepted: 16 November 2016; Published: 23 November 2016 Abstract: Two novel thiosemicarbazones and eight novel 2-{[1-(5-alkyl/arylalkylpyrazin-2-yl) ethylidene]hydrazono}-1,3-thiazolidin-4-ones were prepared and tested against a panel of eight fungal strains–Candida albicans ATCC 44859, Candida tropicalis 156, Candida krusei E 28, Candida glabrata 20/I, Trichosporon asahii 1188, Aspergillus fumigatus 231, Lichtheimia corymbifera 272, and Trichophyton interdigitale 445. 1,3-Thiazolidin-4-ones exhibited activity against all strains, the most potent derivative was 2-{[1-(5-butylpyrazin-2-yl)ethylidene]hydrazono}e-1,3-thiazolidin-4-one. Susceptibility of C. glabrata to the studied 1,3-thiazolidin-4-ones (minimum inhibitory concentrations (MICs) were in the range 0.57 to 2.78 mg/L) is of great interest as this opportunistic pathogen is poorly susceptible to azoles and becomes resistant to echinocandins. Antifungal potency of thiosemicarbazones was slightly lower than that of 1,3-thiazolidin-4-ones. Keywords: acetylpyrazine; thiosemicarbazones; 1,3-thiazolidin-4-ones; antifungal; Candida glabrata 1. Introduction Fungal infections, especially invasive ones, represent a serious problem. Whilst topical fungal diseases are quite common and cause considerable morbidity, they are generally not life-threatening [1]. On the contrary, it has been estimated that invasive fungal infections are responsible for the deaths of 1.5 million people each year [2]. The increased incidence of life threatening systemic fungal infections is mainly due to the increasing numbers of immunocompromised people [2,3]. Besides, infections that were once uncommon emerge more frequently in the United States and Europe as a result of international travel, immigration from endemic areas, and changing climate conditions [4]. Fungal resistance also prevents successful treatment of mycoses [5–8]. Therefore, searching for new drugs and therapeutic options is of high importance [9–11]. Molecules 2016, 21, 1592; doi:10.3390/molecules21111592 www.mdpi.com/journal/molecules