Acta Pharm. 62 (2012) 221-236

 

full paper

Original research paper

 

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

BEATRIZ C. C. SOUZA, TIAGO B. DE OLIVEIRA, THIAGO M. AQUINO, MARIA C. A. DE LIMA, IVAN R. PITTA, SUELY L. GALDINO, EDELTRUDES O. LIMA, TERESINHA GON ALVES-SILVA, GARDÊNIA C. G. MILITÃO, LUCIANA SCOTTI, MARCUS T. SCOTTI and FRANCISCO J. B. MENDON A Jr.

franciscojbmendonca@yahoo.com.br

1 Departamento de Antibi ticos, Universidade Federal de Pernambuco, Recife-PE 50670-910,Brazil

2 Departamento de Ciências Farmacêuticas, Universidade Federal da Para ba, João Pessoa-PB, 58051-970, Brazil

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

4 Departamento de Ciências Biol gicas, Universidade Estadual da Para ba, CCBSA, João Pessoa-PB 58070-450, Brazil

Accepted April 27, 2012

 

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 Criptococcusneoformans and for their antiproliferative activity against a panel of 3 human cancer cell lines (HT29, NCI H-292 and HEP). Forantiproliferative 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 forantiproliferative 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.

 

Keywords: cycloalkyl[b]thiophene derivatives, antifungal activity, antiproliferative activity, PLS-DA, Pentacle program