Preliminary antifungal and cytotoxic evaluation of synthetic cycloalkyl[b]thiophene derivatives with PLS-DA analysis.
Acta Pharm
; 62(2): 221-36, 2012 Jun.
Article
in En
| MEDLINE
| ID: mdl-22750820
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiophenes
/
Drug Design
/
Bridged Bicyclo Compounds, Heterocyclic
/
Fungi
/
Indoles
/
Antifungal Agents
/
Neoplasms
/
Antineoplastic Agents
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Acta Pharm
Journal subject:
FARMACIA
/
FARMACOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
Brazil