Synthesis and biological evaluation of novel 1,3,4‐oxadiazole derivatives as anticancer agents and potential EGFR inhibitors

Abstract

EGFR (epidermal growth factor receptor) tyrosine kinases are frequently used in recent years, especially in small cell lung cancer. As with all other anticancer drugs, problems such as high side‐effect profiles and resistance to anticancer drugs call for new antiproliferative compounds. In the light of the above information, novel quinoxalin‐oxadiazole derivatives were synthesized as EGFR inhibitors in this study. Synthesis of compounds (3a–3j) was performed according to the literature methods. Their structures were elucidated by 1H‐NMR, 13C‐NMR, and HRMS spectroscopic methods. Structure elucidation was performed for compound 3e using 2D NMR technique. MTT test was performed to assess the cell proliferation effects of the different compounds on lung and mammary cell lines (A549, MCF7). In addition, obtained compounds (3a–3j) were screened against healthy CCD19‐Lu cell line (human lung fibroblast normal cells) to determine selectivity of the cytotoxic activities. Among the tested compounds, 3e and 3j showed significant cytotoxic activity against A549 cancer cell. Moreover, compound 3g and 3h displayed good activity. And the compounds 3e and 3j performed significant EGFR inhibition. Interaction modes of the compounds 3e, 3j were investigated against EGFR tyrosine kinase by means of docking studies. As a result of the studies, the importance of the quinoxaline ring and the NO2 substituent has been understood. In future studies, it is planned to make modifications by keeping these two structures constant. The activity can be contributed by using other heterocyclic rings instead of the oxadizaole ring.

Synthesis of ursolic acid arylidene-hydrazide hybrid compounds and investigation of their cytotoxic and antimicrobial effects

“…All the experiments were carried out in triplicates, and the results were presented as a mean ± standard deviation. The concentration-dependent graph was drawn by comparing the data for each substance whose measurement was repeated at least 3 times, and the relative % cell viability was determined (Haselsberger et al 1996;Kumar et al 2018;Meran et al 2018;Senol H. et al 2020;Osmaniye et al 2021).…”

Metallo‐phthalocyanines Containing 1,3,4‐oxadiazole Substituents: Synthesis, Characterization, Electrochemical and Spectroelectrochemical Properties

“…They have attracted the attention of researchers because they give a wide variety of reactions [15] . Thanks to their important therapeutic effects, they are used in antiviral, antioxidant, antimicrobial, antidiabetic and enzyme inhibitor applications effectively [16–18] . In addition to these pharmacological properties, oxadiazoles containing π electrons are used in electrochemical applications such as corrosion inhibition, organic optoelectronics and electropolymerization thanks to their redox richness [19–21] …”

“…[15] Thanks to their important therapeutic effects, they are used in antiviral, antioxidant, antimicrobial, antidiabetic and enzyme inhibitor applications effectively. [16][17][18] In addition to these pharmacological properties, oxadiazoles containing π electrons are used in electrochemical applications such as corrosion inhibition, organic optoelectronics and electropolymerization thanks to their redox richness. [19][20][21] The aim of this study is to prepare new compounds with high potential for use in the field of electrochemistry by derivatizing phthalocyanine complexes that carry redox active center metal and thus have the potential for electrochemistry applications with an oxadiazole compound with electrochemical activity.…”

Copper‐Catalyzed Synthesis of O/N‐Alkyl S‐Phenyl Phenylcarbamothioates: An Odorless and Chemo‐selective Chan–Lam Reaction to Construct C−S Bond

“…Compound b (Figure 1b) is a novel and highly efficient non‐nucleoside HIV‐1 reverse transcriptase inhibitor for the treatment of HIV infection [7] . Besides, the central fragment has been used in various antiviral, [8] antioxidant, [9] and anticancer active [10] drug molecules (Figure 1c, Figure 1d, Figure 1e).…”