Recent Advances in the Synthesis of Polyamine Derivatives and Their Applications

Biogenic polyamines (PAs) are involved in the growth and development of normal cells, and their intracellular concentration is stable. The concentration of PAs in cancer cells is significantly increased to promote and sustain their rapid proliferation. Over the years, synthetic PAs, which differ in their structure, have demonstrated high antitumor activity and are involved in clinical trials. The chemical synthesis of PAs and their conjugates require the correct choice of synthetic pathways—methods for constructing conjugates and the orthogonal protection of amino groups. The most common methods of synthesis of PA conjugates are acylation of regioselectively protected PAs or their alkylation under the conditions of the Fukuyama reaction. One of the most promising methods of PA synthesis is the use of a multicomponent Ugi reaction, which allows various PAs to be obtained in high yields. In this review, we describe and analyze various approaches that are used in the synthesis of polyamines and their conjugates.     

Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH₃. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.     

Nearest-Neighbour and Non-Nearest-Neighbour Non-Covalent Interactions between Substituents in the Aromatic Systems: Experimental and Theoretical Investigation of Functionally Substituted Benzophenones

Benzophenone derivatives exhibit not only biological activity but also act as photo initiator and UV blocker. We carried out experimental and theoretical thermochemical studies of hydroxy- and methoxy-substituted benzophenones. Standard molar enthalpies of vaporisation were obtained from the temperature dependence of vapour pressures measured by the transpiration method. The thermodynamic data on phase transitions available in the literature (crystal–gas, crystal–liquid, and liquid–gas) were also collected and evaluated. High-level quantum chemical methods G3MP2 and G4 were used to estimate the standard molar enthalpies of formation of substituted benzophenones in the gas phase and establish agreement between experimental and theoretical results. The application of the “centrepiece” group-contribution approach to hydroxy- and methoxy-substituted benzophenones was demonstrated. A quantitative assessment of the hydrogen bond was carried out using various approaches based on experimental data and quantum chemical calculations.     

Chemical Equilibrium for the Reacting System Acetic Acid–Ethanol–Ethyl Acetate–Water at 303.15 K, 313.15 K and 323.15 K

The chemical equilibrium (CE) for the quaternary reacting system ethanol–acetic acid–ethyl acetate–water was studied at 303.15, 313.15 and 323.15 K and atmospheric pressure. The CE compositions were determined by gas chromatography and nuclear magnetic resonance analytical methods. The thermodynamic constants of CE at 303.15, 313.15 and 323.15 K were calculated based on the obtained experimental data with the use of the NRTL model.     

Kinetic Analysis of Prostate-Specific Antigen Interaction with Monoclonal Antibodies for Development of a Magnetic Immunoassay Based on Nontransparent Fiber Structures

Prostate cancer is the second most common cancer diagnosed in men worldwide. Measuring the prostate-specific antigen (PSA) is regarded as essential during prostate cancer screening. Early diagnosis of this disease relapse after radical prostatectomy requires extremely sensitive methods. This research presents an approach to development of an ultrasensitive magnetic sandwich immunoassay, which demonstrates the limit of PSA detection in human serum of 19 pg/mL at a dynamic range exceeding 3.5 orders of concentration. Such attractive performance stems, inter alia, from the kinetic analysis of monoclonal antibodies (mAbs) against free PSA to select the mAbs exhibiting best kinetic characteristics and specificity. The analysis is carried out with a label-free multiplex spectral-correlation interferometry compatible with inexpensive single-use glass sensor chips. The high sensitivity of developed PSA immunoassay is due to electronic quantification of magnetic nanolabels functionalized by the selected mAbs and three-dimension porous filters used as an extended solid phase. The assay is promising for PSA monitoring after radical prostatectomy. The proposed versatile approach can be applied for the rational design of highly sensitive tests for detection of other analytes in many fields, including in vitro diagnostics, veterinary, food safety, etc.     

pH-Dependent Photoinduced Interconversion of Furocoumaric and Furocoumarinic Acids

Photo-controlled or photo-regulated molecules, especially biologically active and operating in physiological conditions, are in steady demand. Herein, furocoumaric and furocoumarinic acids being (Z/E)-isomers relative to each other were obtained in two stages starting from psoralen: the alkaline solvolysis of psoralen led to furocoumaric acid, which was further Z → E photoisomerized (365 nm) to furocoumarinic acid. The kinetics of Z → E photoisomerization was monitored by HPLC and UV-vis spectrophotometry. Photophysical characteristics in the aqueous phase for both acids, as well as the reversibility of (Z/E) photoisomerization process, were also assessed. Furocoumarinic acid was found to be visibly fluorescent at pH 2.0–12.0, with the maxima of fluorescence emission spectra being pH-dependent. The reverse E → Z photoisomerization predicted by quantum chemistry calculations as energetically favorable for the monoanionic form of furocoumarinic acid was proved in the experiment while being complicated by pyrone ring closure back to psoralen in acidic and neutral conditions. The preparative synthesis of furocoumarinic acid outlined in this work is particularly valuable in view of a wide range of pharmacological effects previously predicted for this compound.     

Synthesis of novel lipophilic tetraamines with cytotoxic activity

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New Approaches to the Synthesis of 2,2′: 6′,2″-Terpyridine and Some of Its Derivatives

A new two-step procedure has been developed for the synthesis of 2,2′: 6′,2″-terpyridine and 4′-methylsulfanyl-2,2′: 6′,2″-terpyridine in more than 70% yield on the basis of Potts’ condensation. Efficient methods have been proposed for purification of all condensation products.