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

• Main Authors: Krzysztof Szafrański, Jarosław Sławiński, Łukasz Tomorowicz, Anna Kawiak
• Format: Article
• Language: English
• Published: MDPI AG 2020-03-01
• Series: International Journal of Molecular Sciences
• Subjects: benzenesulfonamide; synthesis; 1,3,4-oxadiazole; anticancer activity; qsar; cluster analysis
• Online Access: https://www.mdpi.com/1422-0067/21/6/2235

To learn more about the structure&#8722;activity relationships of (<i>E</i>)-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 (<i>E</i>)-5-[(5-(2-arylvinyl)-1,3,4-oxadiazol-2-yl)]-4-chloro-2-R¹-benzenesulfonamides <b>7</b>&#8722;<b>36</b> as well as (<i>E</i>)-4-[5-styryl1,3,4-oxadiazol-2-yl]benzenesulfonamides <b>47</b>&#8722;<b>50</b> and (<i>E</i>)-2-(2,4-dichlorophenyl)-5-(2-arylvinyl)-1,3,4-oxadiazols <b>51</b>&#8722;<b>55</b>. 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 <b>31</b>, 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 &#181;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 <i>meta</i> 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&#8722;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.