A series of 2-(arylidene)amino-cycloalkylbthiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (1a-c). The title compounds were screened for their antifungal activity against Candida krusei and Criptococcus neoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). For antiproliferative activity, the partial least squares (PLS) methodology was applied. Some of the prepared compounds exhibited promising antifungal and proliferative properties. The most active compounds for antifungal activity were cyclohexylbthiophene derivatives, and for antiproliferative activity cycloheptylbthiophene derivatives, especially 2-(1H-indol-2-yl-methylidene)amino- 5,6,7,8-tetrahydro-4H-cycloheptabthiophene-3-carbonitrile (2r), which inhibited more than 97 % growth of the three cell lines. The PLS discriminant analysis (PLS-DA) applied generated good exploratory and predictive results and showed that the descriptors having shape characteristics were strongly correlated with the biological data. Koristeći supstituirane aromatske aldehide u Gewaldovim aduktima 1a-c sintetizirani su derivati 2-(ariliden)amino-cikloalkilbtiofen-3-karbonitrila (2a-x). Ispitano je antimikotsko djelovanje tih spojeva na gljivice Candida krusei i Criptococcus neoformans te antiproliferativno djelovanje na tri humane tumorske stanične linije (HT29, NCI H-292 i HEP). Za antiproliferativno djelovanje primijenjena je metoda parcijalnih najmanjih kvadrata (PLS) koristeći softverski program Pentacle. Neki od ispitanih spojeva pokazuju obećavajuće antimikotsko i antiproliferativno djelovanje. Najjače antimikotsko djelovanje imaju cikloheksilbtiofen derivati, a najjače antiproliferativno djelovanje cikloheptilbtiofen derivati, posebice 2-(1H-indol-2-il-metiliden)amino-5,6,7,8-tetrahidro-4H-cikloheptabtiofen-3-karbonitril (2r), koji inhibira više od 97 % rast svih triju ispitivanih staničnih linija. Primijenjena PLS diskriminirajuća analiza dala je dobre istraživačke i prognostičke rezultate i pokazala da deskriptori dobro koreliraju s biološkim rezultatima.