Influence of the molecular structure of macrocyclic pyridinophanes, their analogues and some other compounds on anticancer activity (Leukemia, central nervous system (CNS) cancer, prostate cancer, breast cancer, melanoma, non-small cell lung cancer, colon cancer, ovarian cancer, renal cancer) was investigated by means of a new 4D-QSAR approach based on the simplex representation of molecular structures (SiRMS). For all the investigated molecules, the 3D structural models were first created and the set of conformers (fourth dimension) was used. Each conformer was represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry). Statistic characteristics of the QSAR partial least squares (PLS) models were satisfactory (correlation coefficient r=0.990-0.861; cross-validation coefficient CVR=0.914-0.633). The molecular fragments increasing and decreasing anticancer activity were defined. This information may be useful for the design and direct synthesis of novel anticancer agents.

This review explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in antiviral research. We provide an introduction to and description of SiRMS, its application in antiviral research and future directions of development of the Simplex approach and the whole QSAR field. In the Simplex approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry). The main advantages of SiRMS are consideration of the different physical-chemical properties of atoms, high adequacy and good interpretability of models obtained and clear procedures for molecular design. The reliability of developed QSAR models as predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic and biological experiments. The SiRMS approach is realized as the complex of the computer program 'HiT QSAR', which is available on request.

6-azacytidine demonstrates activity against adenoviruses types 1, 2, 5. It inhibit synthesis of viral DNA and proteins. 6-AC shows antiherpetic and antiinfluenza action during experimental infection in mice. 6-AC is prospective for drug development as an antiviral substance with a wide spectrum of activity.

Quantitative estimation of the structure-anticancer activity relationship in a series of macrocyclic Schiff bases of 2,6-bis(formylaryloxymethyl)pyridines was carried out by the topological approach. Correlation equations describing the relationship between the anticancer activity and structural parameters of the molecules studied and descriptors characterizing their structure were obtained on the basis of in vitro screening data. The influence of structure of the investigated substances as reflected by the parameters studied on the anticancer activity, was established.

A new 4D-QSAR approach has been considered. For all investigated molecules the 3D structural models have been created and the set of conformers (fourth dimension) have been used. Each conformer is represented as a system of different simplexes (tetratomic fragments of fixed structure, chirality and symmetry).The investigation of influence of molecular structure of macrocyclic pyridinophanes, their analogues and certain other compounds on anticancer and antiviral (anti-influenza, antiherpes and antiadenovirus) activity has been carried out by means of the 4D-QSAR. Statistic characteristics for QSAR of PLS (partial least squares) models are satisfactory (R = 0.92-0.97; CVR = 0.