Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis
Autor: | Ivan da Rocha Pitta, Teresinha Gonçalves-Silva, Luciana Scotti, Edeltrudes de Oliveira Lima, Marcus Tullius Scotti, Beatriz C. C. Souza, Thiago Mendonça de Aquino, Tiago Bento de Oliveira, Maria C. A. Lima, Gardenia C.G. Militão, Francisco Jaime Bezerra Mendonça, Suely Lins Galdino |
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Rok vydání: | 2012 |
Předmět: |
Antifungal
Antifungal Agents Indoles Stereochemistry medicine.drug_class Pharmaceutical Science Antineoplastic Agents Microbial Sensitivity Tests Thiophenes Adduct Structure-Activity Relationship Cell Line Tumor Neoplasms Candida krusei Nitriles medicine Humans Transition Temperature Cytotoxic T cell Least-Squares Analysis Candida Cell Proliferation Pharmacology Molecular Structure biology Chemistry Fungi Discriminant Analysis General Medicine Bridged Bicyclo Compounds Heterocyclic biology.organism_classification Thiophene derivatives Drug Design Cryptococcus neoformans Human cancer |
Zdroj: | Acta Pharmaceutica. 62:221-236 |
ISSN: | 1846-9558 1330-0075 |
Popis: | Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysisA 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 againstCandida kruseiandCriptococcus neoformansand 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. |
Databáze: | OpenAIRE |
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