4-(Benzoxazol-2-yl)phenyl 3-((3-Chloro-1,4-Naphthoquinon-2-yl)amino)phenyl Sulfate

Aseeva N.V., Danilenko N.V., Plotnikov E.V., Korotkova E.I., Lipskikh O.I., Solomonenko A.N., Erkovich A.V., Eskova D.D., Khlebnikov A.I.

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.

Navarro-Tovar G., Vega-Rodríguez S., Leyva E., Loredo-Carrillo S., de Loera D., López-López L.I.

Natural product derivatives are essential in searching for compounds with important chemical, biological, and medical applications. Naphthoquinones are secondary metabolites found in plants and are used in traditional medicine to treat diverse human diseases. Considering this, the synthesis of naphthoquinone derivatives has been explored to contain compounds with potential biological activity. It has been reported that the chemical modification of naphthoquinones improves their pharmacological properties by introducing amines, amino acids, furan, pyran, pyrazole, triazole, indole, among other chemical groups. In this systematic review, we summarized the preparation of nitrogen naphthoquinones derivatives and discussed their biological effect associated with redox properties and other mechanisms. Preclinical evaluation of antibacterial and/or antitumoral naphthoquinones derivatives is included because cancer is a worldwide health problem, and there is a lack of effective drugs against multidrug-resistant bacteria. The information presented herein indicates that naphthoquinone derivatives could be considered for further studies to provide drugs efficient in treating cancer and multidrug-resistant bacteria.

Sattar R., Mukhtar R., Atif M., Hasnain M., Irfan A.

Schepetkin I.A., Karpenko A.S., Khlebnikov A.I., Shibinska M.O., Levandovskiy I.A., Kirpotina L.N., Danilenko N.V., Quinn M.T.

Cell division cycle 25 (Cdc25) and mitogen-activated protein kinase kinase 7 (MKK7) are enzymes involved in intracellular signaling but can also contribute to tumorigenesis. We synthesized and characterized the biological activity of 1,4-naphthoquinones structurally similar to reported Cdc25 and(or) MKK7 inhibitors with anticancer activity. Compound 7 (3-[(1,4-dioxonaphthalen-2-yl)sulfanyl]propanoic acid) exhibited high binding affinity for MKK7 (Kd = 230 nM), which was greater than the affinity of NSC 95397 (Kd = 1.1 μM). Although plumbagin had a lower binding affinity for MKK7, this compound and sulfur-containing derivatives 4 and 6-8 were potent inhibitors of Cdc25A and Cdc25B. Derivative 22e containing a phenylamino side chain was selective for MKK7 versus MKK4 and Cdc25 A/B, and its isomer 22f was a selective inhibitor of Cdc25 A/B. Docking studies performed on several naphthoquinones highlighted interesting aspects concerning the molecule orientation and hydrogen bonding interactions, which could help to explain the activity of the compounds toward MKK7 and Cdc25B. The most potent naphthoquinone-based inhibitors of MKK7 and/or Cdc25 A/B were also screened for their cytotoxicity against nine cancer cell lines and primary human mononuclear cells, and a correlation was found between Cdc25 A/B inhibitory activity and cytotoxicity of the compounds. Quantum chemical calculations using BP86 and ωB97X-D3 functionals were performed on 20 naphthoquinone derivatives to obtain a set of molecular electronic properties and to correlate these properties with cytotoxic activities. Systematic theoretical DFT calculations with subsequent correlation analysis indicated that energy of the lowest unoccupied molecular orbital E(LUMO), vertical electron affinity (VEA), and reactivity index ω of these molecules were important characteristics related to their cytotoxicity. The reactivity index ω was also a key characteristic related to Cdc25 A/B phosphatase inhibitory activity. Thus, 1,4-naphthoquinones displaying sulfur-containing and phenylamino side chains with additional polar groups could be successfully utilized for further development of efficacious Cdc25 A/B and MKK7 inhibitors with anticancer activity.

Barrow A.S., Smedley C.J., Zheng Q., Li S., Dong J., Moses J.E.

SuFEx (Sulfur Fluoride Exchange) is a modular, next generation family of click reactions, geared towards the rapid and reliable assembly of functional molecules.

Singh S., Veeraswamy G., Bhattarai D., Goo J., Lee K., Choi Y.

In recent years, the emergence of biologically active compounds that contain a heterocyclic ring has gained a great deal of attention among medicinal chemists. Among these, benzoxazole-based compounds are particularly attractive because of their wide range of pharmacological activities. In this focus review, we highlight recent advancements in the development of benzoxazole-based pharmacologically active compounds since the year 2000.

Dong J., Krasnova L., Finn M.G., Sharpless K.B.

AbstractAryl sulfonyl chlorides (e.g. Ts‐Cl) are beloved of organic chemists as the most commonly used SVI electrophiles, and the parent sulfuryl chloride, O2SVICl2, has also been relied on to create sulfates and sulfamides. However, the desired halide substitution event is often defeated by destruction of the sulfur electrophile because the SVICl bond is exceedingly sensitive to reductive collapse yielding SIV species and Cl−. Fortunately, the use of sulfur(VI) fluorides (e.g., R‐SO2‐F and SO2F2) leaves only the substitution pathway open. As with most of click chemistry, many essential features of sulfur(VI) fluoride reactivity were discovered long ago in Germany.6a Surprisingly, this extraordinary work faded from view rather abruptly in the mid‐20th century. Here we seek to revive it, along with John Hyatt’s unnoticed 1979 full paper exposition on CH2CH‐SO2‐F, the most perfect Michael acceptor ever found.98 To this history we add several new observations, including that the otherwise very stable gas SO2F2 has excellent reactivity under the right circumstances. We also show that proton or silicon centers can activate the exchange of SF bonds for SO bonds to make functional products, and that the sulfate connector is surprisingly stable toward hydrolysis. Applications of this controllable ligation chemistry to small molecules, polymers, and biomolecules are discussed.

Saluja P., Sharma H., Kaur N., Singh N., Jang D.O.

We synthesized an imine-linked, benzimidazole-based chemosensor that can be used for chromogenic recognition of Mg 2+ and fluorescent recognition of Cr 3+ . The chemosensor shows sensitive, selective, and ratiometric recognition of Cr 3+ through concurrent quenching at one wavelength and enhancement of fluorescence intensity at another wavelength. It can also be used to detect Mg 2+ via UV–vis absorption spectroscopy. DFT calculations support these phenomena. The sensor can be used to strain microbe cells without breakage.

Murty M.S., Ram K.R., Rao R.V., Yadav J.S., Rao J.V., Cheriyan V.T., Anto R.J.

The synthesis and cytotoxic activity studies of a new series of cyclic amine containing benzoxazole and benzoxazolone derivatives are described. The 2-cyclic amine-1,3-benzoxazoles 5a–k, 5-chloro-3-(3-chloropropyl)-1,3-benzoxazol-2(3H)-one 8 and 3-[3-(cyclic amino)propyl]-1,3-benzoxazol-2(3H)-ones 9a–f were synthesized. The newly synthesized compounds with the influence of the presence of cyclic amine moiety in the benzoxazole scaffold have been evaluated with respect to their cytotoxic effect toward four human cancer cell lines. The new compounds were evaluated to see whether substitution at the second and third position of the benzoxazole motif influence their cytotoxic effect toward cancer cells.

Uchimiya M., Stone A.T.

The role of quinone biomolecules and quinone moieties of natural organic matter (NOM) as the electron transfer mediator in essential biogeochemical processes such as iron bioreduction and contaminant degradation has received considerable interests in the past decade. Hypothesized electron shuttling mechanism must be evaluated based on the availability and stability of quinones under a given environmental setting. The goal of this review is to examine the source, reactivity, and fate of potential quinone catalysts with respect to chemical interactions (e.g., with other quinones and nucleophiles) that will inevitably occur in complex environmental media. We will first discuss natural and anthropogenic sources of quinones in aqueous environments, and fundamental transformation pathways including cross reaction, autoxidation, and addition reactions. We will then assess how the described sources (molecular structure) and transformation pathways (stability) will impact the ability of a quinone molecule to catalyze a biogeochemical process. Thermodynamics and kinetics of electron transfer reactions with both the electron donor (e.g., hydrogen sulfide as a bulk reductant) and the terminal electron acceptor (e.g., nitroaromatic explosives in contaminant degradation), and stability towards irreversible side reactions are the key factors determining the geochemical conditions under which the catalysis by a quinone molecule will be operative.

So Y., Heeschen J.P.

The mechanism of 2-phenylbenzoxazole formation from benzoic acid and o-aminophenol in polyphosphoric acid (PPA) is studied by NMR spectroscopy and chemical analysis. Benzoic acid reacts with PPA to form benzoic−phosphoric anhydride and benzoic−polyphosphoric anhydride. The ratio of mixed anhydride to free carboxylic acid increases dramatically as the P2O5 content of PPA increases, but this ratio is independent of reaction temperature and time. When o-aminophenol dissolves in PPA, part of the hydroxyl group is converted to phosphate ester, and only protonated amine is detected. Benzoic acid, mixed anhydride, and PPA are in dynamic equilibrium, and so are PPA, o-aminophenol, and its phosphate ester. The mixed anhydride and o-aminophenol react to form 2-aminophenyl benzoate as the first reaction intermediate which undergoes rapid acyl migration to generate 2-hydroxybenzanilide. Ring closure of 2-hydroxybenzanilide to form 2-phenylbenzoxazole is acid catalyzed. The reactive components in phosphorus pentoxide−...

Hein D.W., Alheim R.J., Leavitt J.J.