Synthesis, Anticancer Evaluation and Structure-Activity Analysis of Novel (E)- 5-(2-Arylvinyl)-1,3,4-oxadiazol-2-yl)benzenesulfonamides

Autor: Anna Kawiak, Jarosław Sławiński, Łukasz Tomorowicz, Krzysztof Szafrański
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Quantitative structure–activity relationship
synthesis
Stereochemistry
Substituent
Antineoplastic Agents
Chemistry Techniques
Synthetic
01 natural sciences
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
HeLa
Structure-Activity Relationship
03 medical and health sciences
chemistry.chemical_compound
Meta
0302 clinical medicine
Cell Line
Tumor
Molecular descriptor
1
3
4-oxadiazole
Humans
Moiety
Physical and Theoretical Chemistry
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Cell Proliferation
chemistry.chemical_classification
Sulfonamides
Dose-Response Relationship
Drug
Molecular Structure
biology
010405 organic chemistry
QSAR
Organic Chemistry
General Medicine
biology.organism_classification
In vitro
0104 chemical sciences
Computer Science Applications
Sulfonamide
benzenesulfonamide
anticancer activity
lcsh:Biology (General)
lcsh:QD1-999
chemistry
030220 oncology & carcinogenesis
cluster analysis
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 6
International Journal of Molecular Sciences, Vol 21, Iss 6, p 2235 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21062235
Popis: To learn more about the structure&ndash
activity relationships of (E)-3-(5-styryl-1,3,4-oxadiazol-2-yl)benzenesulfonamide derivatives, which in our previous research displayed promising in vitro anticancer activity, we have synthesized a group of novel (E)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R1-benzenesulfonamides 7-36 as well as (E)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides 47-50 and (E)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols 51-55. All target derivatives were evaluated for their anticancer activity on HeLa, HCT-116, and MCF-7 human tumor cell lines. The obtained results were analyzed in order to explain the influence of a structure of the 2-aryl-vinyl substituent and benzenesulfonamide scaffold on the anti-tumor activity. Compound 31, bearing 5-nitrothiophene moiety, exhibited the most potent anticancer activity against the HCT-116, MCF-7, and HeLa cell lines, with IC50 values of 0.5, 4, and 4.5 µ
M, respectively. Analysis of structure-activity relationship showed significant differences in activity depending on the substituent in position 3 of the benzenesulfonamide ring and indicated as the optimal meta position of the sulfonamide moiety relative to the oxadizole ring. In the next stage, chemometric analysis was performed basing on a set of computed molecular descriptors. Hierarchical cluster analysis was used to examine the internal structure of the obtained data and the quantitative structure&ndash
activity relationship (QSAR) analysis with multiple linear regression (MLR) method allowed for finding statistically significant models for predicting activity towards all three cancer cell lines.
Databáze: OpenAIRE
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