QSAR-modeling of desoxyuridine triphosphatase inhibitors in a series of some derivatives of uracil

Abstract

Due to the widespread prevalence, deoxyuridine triphosphatase (UTPase) is considered by modern biochemists and physicians as a promising target for the development of drugs with a wide range of activities. The therapeutic effect of these drugs will be due to suppression of DNA biosynthesis in various viruses, bacteria and protozoa. In order to rationalize the search for new dUTPase inhibitors, domestic and foreign researchers are actively using the QSAR methodology at the selection stage of hit compounds. However, the practical application of this methodology is impossible without existence of valid QSAR models. With the use of the GUSAR 2013 program, a quantitative analysis of the relationship between the structure and efficacy of 135 dUTPase inhibitors based on uracil derivatives was performed in the IC50 range of 30¸185000 nmol/L. Six statistically significant valid consensus models, characterized by high descriptive ability and moderate prognostic ability on the structures of training and test samples, are constructed. To build valid QSAR models for dUTPase inhibitors can use QNA or MNA descriptors and their combinations in a consensus approach.

QSAR Assessing the Efficiency of Antioxidants in the Termination of Radical-Chain Oxidation Processes of Organic Compounds

“…Note that compound 8-PPDA has already used as an antioxidant in composite synthetic rubbers [ 67 ]. However, its antioxidant activity using classical model reactions of liquid-phase oxidation of ethylbenzene or cumene has not been studied.…”

QSPR Modeling and Experimental Determination of the Antioxidant Activity of Some Polycyclic Compounds in the Radical-Chain Oxidation Reaction of Organic Substrates

“…The QSPR modeling of the derivatives of the sulfur-containing alkylphenols, natural phenols, chromane and lupane acids, betulonic and betulinic acids, and 20-hydroxyecdysone with general structural formulas I – VIII ( Figure 1 ) was performed using the GUSAR2019 (General Unrestricted Structure Activity Relationships) software [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ].…”

“…The M1–M6 QSPR models were built based on two types of substructural descriptors of atomic neighborhoods: QNA (quantitative neighbourhoods of atoms) and MNA (multilevel neighbourhoods of atoms) [ 11 , 12 , 17 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 ]. The calculation of these types of descriptors in the GUSAR2019 program was performed automatically from the structural formulas of chemical compounds, taking into account the valence and partial charges of all atoms.…”

“…One of the programs used to calculate the physico-chemical and structural descriptors, to select the most significant of them, and to build consensus QSPR models based on them is the GUSAR2019 (General Unrestricted Structure Activity Relationships) program and its earlier versions GUSAR2013 and GUSAR2011 [ 11 , 12 , 17 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ]. This program has proven efficient in the modeling of various types of biological activities for some heterogeneous organic compounds [ 54 , 55 , 56 , 57 , 61 , 62 ]. In our pioneering work [ 62 , 63 , 64 , 65 , 66 ], we reported the use of an earlier version of the program, GUSAR2013, for the QSPR modeling of antioxidants in the series of some phenols, amines, uracils, benzopyrans, and benzofurans.…”

“…This program has proven efficient in the modeling of various types of biological activities for some heterogeneous organic compounds [ 54 , 55 , 56 , 57 , 61 , 62 ]. In our pioneering work [ 62 , 63 , 64 , 65 , 66 ], we reported the use of an earlier version of the program, GUSAR2013, for the QSPR modeling of antioxidants in the series of some phenols, amines, uracils, benzopyrans, and benzofurans. In doing so, the statistically significant valid models were constructed to predict the oxidation chain termination rate constants of logk 7 , in order to search for new potentially effective antioxidants in virtual libraries and databases.…”