Biophysical investigations of molecular mechanisms of action of chemotherapeutic agents. 2. Antimicrobial and antimalarial agents (Review)

Background: Getting information on molecular mechanisms of action of biologically active compounds is a necessary step in the elaboration of new medicines. The development and application of molecular-biophysical experimental and theoretical techniques are required to establish the mechanisms of interaction of chemotherapeutic drugs, which affect infectious agents, with their potential molecular targets in biological objects. Objectives: The aim of this review is a generalization of the results of long-term investigations on molecular mechanisms of action of chemotherapeutic agents performed in the biophysical departments of B. Verkin Institute for Low Temperature Physics and Engineering (ILTPE) of the NAS of Ukraine. In the second part of the review the data on the assumed mechanisms of action of some antimicrobial and antimalarial agents are presented. Materials and methods: Experimental methods of soft ionization mass spectrometry and computer simulations by means of quantum chemistry were used in the combined investigations. Results: Model systems composed of chemotherapeutic drugs and their molecular targets were studied, such as antimicrobial drugs and biomembranes components, antimalarial drugs and heme. The mechanisms of action of these chemotherapeutic agents were revealed at the molecular level, which consisted in the noncovalent interactions of the drugs’ molecules or ions with molecular targets resulting in the supramolecular complexes formation. Methods of soft ionization mass spectrometry allowed us to detect such noncovalent complexes of the medicines with biomolecules. Structural, electronic and energetic characteristics of these complexes were established by quantum chemical calculations. Conclusions: The results of investigations conducted during several decades at the ILTPE have demonstrated the efficiency of the application of the methods and approaches of molecular biophysics to determination of molecular mechanisms of chemotherapeutic drugs action. The results obtained are of practical importance for further development of medicines and schemes of their application. A number of the results obtained were included into international data bases.