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.
Highlights
Malignant diseases are one of the major threats to global public health
1 with phenylmethanethiol in the presence of tetrabutylammonium iodide (TBAI) as a phase with phenylmethanethiol in the presence of tetrabutylammonium iodide (TBAI) as a phase transfer transfer catalyst resulted in the selective substitution of chlorine atom in position 2 of the catalyst resulted in the selective substitution of chlorine atom in position 2 of the benzene ring, benzene ring, yielding
13 C NMR spectra were recorded on a Varian Unity Plus 500 apparatus (Varian, Palo Alto, CA, USA), chemical shifts are expressed at δ values relative to Me4 Si (TMS) as an internal standard
Summary
Malignant diseases are one of the major threats to global public health. Based on the GLOBOCAN2018 database, which gathered estimates of incidence and mortality for 36 types of cancer in 185 countries, the number of new cases of cancer in 2018 was estimated to be 18.1 million and the number of deaths from cancer was 9.6 million worldwide [1]. Malignant diseases are one of the major threats to global public health. In 2009, the medical and indirect costs of new cancer cases globally were estimated to be 286 billion $ [2]. Despite advanced work on new methods of cancer therapy such as immunotherapy, nanoscale and nanostructure-based therapeutics or gene therapy, the main methods of choice remain surgery, radiotherapy and chemotherapy [3]. The search for novel small molecule chemotherapeutic drugs is one of the major challenges of modern medicinal chemistry. Sulfonamides as a class of biological active compounds have been widely used since the 1940s, mainly as antibacterial, hypoglycemical, diuretics and antiglucoma drugs.
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