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

Abstract

To learn more about the structure–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 µM, 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–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.

The Physical Chemistry and Chemical Physics (PCCP) Section of the International Journal of Molecular Sciences in Its Publications: The First 300 Thematic Articles in the First 3 Years

“…This area is the largest in terms of the number of related publications and includes 91 articles, namely [ 1 , 2 , 3 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 ,…”

“…The last one seems to be the most detailed, and it is precisely this that we will try to implement in the course of our narrative. As it should be expected, a priori, most of the publications in this direction are devoted to organic compounds, and primarily organic molecules; these include, with varying degrees of correctness, publications [ 1 , 2 , 3 , 102 , 103 , 104 , 106 , 108 , 112 , 117 , 118 , 119 , 121 , 124 , 127 , 128 , 130 , 131 , 132 , 133 , 135 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 146 , 147 , 148 , 151 , 153 , 154 , 156 , 157 , 164 , 165 , 166 , 168 , 171 , 172 , 174 , 176 , 178 , 180 , 183 , 185 , 186 ]. Much less space is occupied by the works related to polymeric (in fact, to a high molecular weight) compounds [ 113 , …”

Synthesis and Characterization of Few New Substituted 1,3,4-Oxadiazoles 1,2,4-Triazoles and Schiff Bases via Chalcone Compounds

“…9 1,3,4-Oxadiazole and its derivatives have great biological properties 10 with many examples in the literature such as antiviral, antifungal, antimicrobial, anti-inflammatory and anticancer activities. [11][12][13][14][15] Moreover, many studies showed that the existence of more than two heterocyclic units may lead to an increase the antimicrobial activity significantly. 16 Schiff bases are compounds carrying azomethine functional group 17 (C=N), Schiff bases obtained from complexes derived heterocycles have a great importance in the field of pharmaceutical industries due to versatile uses in synthetic intermediates and the wide range of biological properties.…”