Persistent inflammation contributes to a number of diseases; therefore, control of the inflammatory response is an important therapeutic goal. In an effort to identify novel anti-inflammatory compounds, we screened a library of pyridazinones and structurally related derivatives that were used previously to identify N-formyl peptide receptor (FPR) agonists. Screening of the compounds for their ability to inhibit lipopolysaccharide (LPS)-induced nuclear factor κB (NF-κB) transcriptional activity in human THP1-Blue monocytic cells identified 48 compounds with anti-inflammatory activity. Interestingly, 34 compounds were FPR agonists, whereas 14 inhibitors of LPS-induced NF-κB activity were not FPR agonists, indicating that they inhibited different signaling pathways. Further analysis of the most potent inhibitors showed that they also inhibited LPS-induced production of interleukin 6 (IL-6) by human MonoMac-6 monocytic cells, again verifying their anti-inflammatory properties. Structure–activity relationship (SAR) classification models based on atom pair descriptors and physicochemical ADME parameters were developed to achieve better insight into the relationships between chemical structures of the compounds and their biological activities, and we found that there was little correlation between FPR agonist activity and inhibition of LPS-induced NF-κB activity. Indeed, Cmpd43, a well-known pyrazolone-based FPR agonist, as well as FPR1 and FPR2 peptide agonists had no effect on the LPS-induced NF-κB activity in THP1-Blue cells. Thus, some FPR agonists reported to have anti-inflammatory activity may actually mediate their effects through FPR-independent pathways, as it is suggested by our results with this series of compounds. This could explain how treatment with some agonists known to be inflammatory (i.e., FPR1 agonists) could result in anti-inflammatory effects. Further research is clearly needed to define the molecular targets of pyridazinones and structurally related compounds with anti-inflammatory activity and to define their relationships (if any) to FPR signaling events.

This study presents the synthesis of new fluorosulfate derivatives of 1,4-naphthoquinone by the SuFEx reaction. Anticancer properties of obtained compounds were studied on PC-3 (prostate adenocarcinoma), SKOV-3 (ovarian cancer), MCF-7 (breast cancer), and Jurkat cell lines. All the studied compounds showed higher cytotoxic effects than Cisplatin. The DFT method was applied to determine the electronic structure characteristics of 1,4-naphthoquinone derivatives associated with cytotoxicity. A method of determination of 2,3-dichloro-1,4-naphthoquinone (NQ), 3-chloro-2-((4-hydroxyphenylamino)-1,4-naphthoquinone (NQ1), and 4-((3-chloro-1,4-naphthoquinon-2-yl)amino)phenyl fluorosulfate (NQS) in a pharmaceutical substance using an impregnated graphite electrode (IMGE) was developed. The morphology of the IMGE surface was studied using scanning electron microscopy (SEM). The electrochemical behavior of NQ, NQ1, and NQS was studied by cyclic voltammetry (CV) in 0.1 M NaClO₄ (96% ethanol solution) at pH 4.0 in a potential range from −1 to +1.2 V. Electrochemical redox mechanisms for the investigated compounds were proposed based on the determining main features of the electrochemical processes. Calibration curves were obtained by linear scan voltammetry in the first derivative mode (LSVFD) with the detection limit (LOD) 7.2 × 10⁻⁶ mol·L⁻¹ for NQ, 8 × 10⁻⁷ mol·L⁻¹ for NQ1, and 8.6 × 10⁻⁸ mol·L⁻¹ for NQS, respectively.

The fluorosulfate derivatives of benzoxazole attract attention since benzoxazole-based compounds have a wide range of biological activities, and the ability of the –SO₂F group to react with various functional groups makes it possible to synthesize various new derivatives. The new 2-(2-(fluorosulfonyloxy)phenyl)benzoxazole (2) has been synthesized by the SuFEx click reaction in a two-chamber reactor. Compound 2 is the first example of a benzoxazole derivative with a fluorosulfate-containing substituent at position two of the benzoxazole heterocycle. The anti-cancer potency of 2 was evaluated in silico using molecular docking. The docking results suggest that title compound 2 is of great interest for further studies as a possible anaplastic lymphoma kinase inhibitor.

In this work, we have studied the physicochemical behaviors of oxidation-reduction of 2,3-dichloro-1,4-naphthoquinone (NQ) and 2-chloro-3-((4-hydroxyphenyl) amino)-1,4-naphthoquinone (NQ1) synthesized on the basis of NQ, on impregnated graphite electrode. The nature of the electrochemical processes was determined and the mechanism of oxidation-reduction of substances was assumed. The operating conditions for the voltammetric determination of compounds on an impregnated graphite electrode were tacc selected, such as the supporting electrolyte - 0.1 M NaClO4 solution in 96% ethanol (pH=2 for NQ, pH=10 for NQ1), V=100 mV.s(-1), as well as the potential and time of accumulation (E-acc +1 V; t(acc) 50 s for NQ and E-acc-1 V; t(acc) 30 s for NQ1). It is shown that the pH of the supporting electrolyte has a high influence on NQ and NQ1 analytical signal. For NQ, the current reaches its maximum value at pH = 2. For NQ1, the opposite effect of pH on the current intensity is observed: the maximum current value is reached at pH = 12. The linear dependence of the reduction peak current at a potential of 0.12 V on the concentration of NQ is observed in the range 2.10(-5) - 8.10(-4) mol.l(-1) with the regression equation I=3.14C - 0.35 (R2=0.9992). For NQ1, the linear range of the calibration curve of the electro oxidation current at a potential of -0.58 V on the concentration is maintained in the range 1.10(-6) - 8.10(-4) mol.l(-1) with regression equation I=45.74C +0.37 (R2=0.9992). The detection limit (LOD) for NQ, calculated according to the 3S criterion, is 7.2.10(-6) mol.l(-1), for NQ1 8.10(-7) The accu- racy of the method of analyzed compounds quantitative determination in the substance was checked by the "spiked test" method.

New 2-(4-(fluorosulfonyloxy)phenyl)benzoxazole (2) was synthesized through the SuFEx click reaction in a two-chamber reactor. The effect of silylation on the yield of the target compound was investigated. The fluorescent properties of compound 2 were determined using experimental and computational methods.

New 4-(benzoxazol-2-yl)phenyl 3-((3-chloro-1,4-naphthoquinon-2-yl)amino)phenyl sulfate was synthesized via the SuFEx click reaction between fluorosulfate-containing 1,4-naphthoquinone and 2-(4-hydroxyphenyl)benzoxazole. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was used as an organic base, while triethylamine was inactive in this reaction.