Dušanka Davidović-Amić

SAR and QSAR of the Antioxidant Activity of Flavonoids

Flavonoids are a group of naturally occurring phytochemicals abundantly present in fruits, vegetables, and beverages such as wine and tea. In the past two decades, flavonoids have gained enormous interest because of their beneficial health effects such as anti-inflammatory, cardio-protective and anticancer activities. These findings have contributed to the dramatic increase in the consumption and use of dietary supplements containing high concentrations of plant flavonoids. The pharmacological effect of flavonoids is mainly due to their antioxidant activity and their inhibition of certain enzymes. In spite of abundant data, structural requirements and mechanisms underlying these effects have not been fully understood. This review presents the current knowledge about structure-activity relationships (SARs) and quantitative structure-activity relationships (QSARs) of the antioxidant activity of flavonoids. SAR and QSAR can provide useful tools for revealing the nature of flavonoid antioxidant action. They may also help in the design of new and efficient flavonoids, which could be used as potential therapeutic agents.

STRUCTURE-ACTIVITY CORRELATION OF FLAVONE DERIVATIVES FOR INHIBITION OF CAMP PHOSPHODIESTERASE

Abstract published in Advance ACS Abstracts, November 1, 1995. 0095-233819511635-1034

THE USE OF THE ORDERED ORTHOGONALIZED MULTIVARIATE LINEAR REGRESSION IN A STRUCTURE-ACTIVITY STUDY OF COUMARIN AND FLAVONOID DERIVATIVES AS INHIBITORS OF ALDOSE REDUCTASE

09.00/0 0 ing various combinations of molecular descriptors. The structures of the flavone derivatives used in this study are shown in Figure 1. A total of 34 descriptors were generated for each flavone derivative. The descriptor pool contained topological and electronic descriptors. The topological descriptors that were calculated include valence connectivity indexes6 0f”’5xv, Wiener number Wand path numbers7 pO-plo, Balaban indexs J, Harary indexes9 HI -&, and molecular topological indexi0 MTI. The electronic descriptors include hardness indexes’ ’ (absolute hardness r, relative hardness qr), energy of the highest occupied molecular orbital E(HOMO), and energy of the lowest unoccupied molecular orbital E(LUMO), topological resonance energy indices’ (topological resonance energy TRE and topological resonance energy per electron TRE(PE)), and the sum of the charges of the atoms located in the chromone moiety

Prediction of pK Values, half-lives and electronic spectra of flavylium salts from molecular structure

The relationship between molecular descriptors and the inhibitory activity of aldose reductase (AR) for a series of coumarin and flavonoid derivatives has been investigated using a novel multivariate linear regression based on the ordered orthogonalized descriptor set. First, starting from the set of 31 descriptors we produced absolutely the best nonorthogonalized QSAR models with I descriptors (I = 1−7). These models are always better than the models that the most authors achieve by the use of the stepwise inclusion-exclusion procedure. In the next step we realized all possible orthogonalization orderings of a given set of N descriptors (there are N! of these). The key result is that some orthogonalization orderings lead to QSAR models with I ordered orthogonalized descriptors that have higher values of both the correlation coefficient R and cross-validated correlation coefficient Rcv than the corresponding models with the same number of nonorthogonalized descriptors. In order to achieve the highest poss...

Experimental and theoretical study of the styrylbenzopyrylium chromophore

Simple QSAR/QSPR models have been developed which enable the prediction of the pK values and half-lives of flavylium salts as a function of their molecular descriptors. On the basis of these results, as well as calculated UV−vis spectra, flavylium salt model structures are proposed, which are expected to be useful as potential food dyes.

QSAR OF FLAVYLIUM SALTS AS INHIBITORS OF XANTHINE OXIDASE

Structural transformations of 7-hydroxy-4′-methoxystyrylbenzopyrylium chloride have been investigated in buffer solutions of pH 2.00–11.00. The reactivity and aromatic stability of this and related styrylbenzopyrylium salts are predicted using standard HMO calculations and the concept of hardness, and correlated with experimental findings. Electronic spectra are calculated using the PPP method. Several model compounds are proposed, which are expected to exhibit high stability and low reactivity, and whose solutions should be red coloured.

Structure-Radical Scavenging Activity Relationships of Flavonoids

A simple QSAR model of xanthine oxidase (XO) inhibitory flavylium salts, which enables prediction of the inhibitory potency of anthocyanidins as a function of their molecular properties, has been developed. The results obtained in the present work help to understand which of the several tautomeric anhydrobase species present in nearly neutral solution are mainly responsible for the inhibition of XO.