title: Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis.
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.
authors: Departamento de Antibióticos, Universidade Federal de Pernambuco, Recife-PE, Brazil.
authors: Beatriz C C
authors: BC
authors: Souza
authors: Tiago B
authors: TB
authors: De Oliveira
authors: Thiago M
authors: TM
authors: Aquino
authors: Maria C A
authors: MC
authors: de Lima
authors: Ivan R
authors: IR
authors: Pitta
authors: Suely L
authors: SL
authors: Galdino
authors: Edeltrudes O
authors: EO
authors: Lima
authors: Teresinha
authors: T
authors: Gonçalves-Silva
authors: Gardênia C G
authors: GC
authors: Militão
authors: Luciana
authors: L
authors: Scotti
authors: Marcus T
authors: MT
authors: Scotti
authors: Francisco J B
authors: FJ
authors: Mendonça
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003455:Cryptococcus neoformans / Q000187:drug effects; D016002:Discriminant Analysis; D015195:Drug Design; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016018:Least-Squares Analysis; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D044366:Transition Temperature
chemical_list: C575880:2-((1H-indol-2-yl-methylidene)amino)-5,6,7,8-tetrahydro-4H-cyclohepta(b)thiophene-3-carbonitrile; D000935:Antifungal Agents; D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007211:Indoles; D009570:Nitriles; D013876:Thiophenes