<abstract xml:lang="en" xmlns="http://www.w3.org/1999/xhtml"><p>A series of 2-[(arylidene)amino]-cycloalkyl[<italic>b</italic>]thiophene-3-carbonitriles (<bold>2a-x</bold>) was synthesized by incorporation of substituted aromatic aldehydes in Gewald adducts (<bold>1a-c</bold>). The title compounds were screened for their antifungal activity against <italic>Candida krusei</italic> and <italic>Criptococcus neoformans</italic> 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 cyclohexyl[<italic>b</italic>]thiophene derivatives, and for antiproliferative activity cycloheptyl[<italic>b</italic>]thiophene derivatives, especially 2-[(1<italic>H</italic>-indol-2-yl-methylidene)amino]- 5,6,7,8-tetrahydro-4<italic>H</italic>-cyclohepta[<italic>b</italic>]thiophene-3-carbonitrile (<bold>2r</bold>), 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.</p></abstract>

A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-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 cyclohexyl[b]thiophene derivatives, and for antiproliferative activity cycloheptyl[b]thiophene derivatives, especially 2-[(1H-indol-2-yl-methylidene)amino]- 5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophene-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.

Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[<italic>b</italic>]thiophene derivatives with PLS-DA analysis

Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife-PE 50670-910, Brazil

Departamento de Ciências Farmacêuticas, Universidade Federal da Paraíba, João Pessoa-PB, 58051-970, Brazil

Departamento de Engenharia e Meio Ambiente, Universidade Federal da Paraíba, Campus IV; Rio Tinto-PB 58297-000, Brazil

Departamento de Ciências Biológicas, Universidade Estadual da Paraíba CCBSA, João Pessoa-PB 58070-450, Brazil

Acta Pharmaceutica

Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[]thiophene derivatives with PLS-DA analysis

A series of 2-[(arylidene)amino]-cycloalkyl[b]thiophene-3-carbonitriles (2a-x) was synthesized by incorporation of substituted aromatic aldehydes in Gewald...

Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis

Pubblicato online: 28 giu 2012

Pagine: 221 - 236

DOI: https://doi.org/10.2478/v10007-012-0017-y

Parole chiave
cikloalkil[]tiofen derivati, antimikotsko djelovanje, antiproliferativno djelovanje, PLS-DA metoda, program Pentacle

This content is open access.