Antioxidant Activity of Pharmaceuticals: Predictive QSAR Modeling for Potential Therapeutic Strategy

Jeličić, Mario-Livio; Kovačić, Jelena; Cvetnić, Matija; Mornar, Ana; Klarić, Daniela Amidžić

doi:10.3390/ph15070791

Cited by 4 publications

(2 citation statements)

References 27 publications

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“…To determine the antioxidant activities, the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) was used, which is considered one of the most widely used methods for measuring the in vitro antioxidant activity of various chemical compounds. This colorimetric method is accurate, easy to perform, and economical, providing a screening of the general activity of the antioxidants and is based on a stable and synthetic radical, DPPH 15 .…”

Section: Resultsmentioning

confidence: 99%

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Hawash

Jaradat

Abualhasan

et al. 2022

Sci Rep

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Previously developed fluorophenyl-isoxazole-carboxamides derivatives were re-synthesized and their scavenging activity against DPPH free radical and inhibitory activity against lipase and α-amylase enzymes were evaluated. The inhibition of the tested enzymes was weak while the most potent activities were observed in the DPPH assay. In particular, compounds 2a and 2c demonstrated high antioxidant potency with IC50 values of 0.45 ± 0.21 and 0.47 ± 0.33 µg/ml, respectively, when compared to Trolox, the positive control compound, which has an IC50 value of 3.10 ± 0.92 µg/ml. Based on the in vitro results, the most potent compound 2a was chosen for in vivo evaluation of antioxidant properties using 20 male mice injected intra-peritoneally and divided into four groups. The in vivo results revealed that total antioxidant capacity (TAC) obtained for mice treated with 2a was two folds greater than that of mice treated with the positive control Quercetin. Although further biological and preclinical investigations need to be performed to assess the therapeutic potential of 2a, the results of this study show promising antioxidant activities both in vitro and in vivo.

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Section: Resultsmentioning

confidence: 99%

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Hawash

Jaradat

Abualhasan

et al. 2022

Sci Rep

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“…When the results of the antioxidant activity of hydrolates are expressed as mM or µM of the TEAC, it is easy to observe and comprehend their potential within the antioxidant context. For example, both test values of TV, SM, and OV can be considered as substantial free radical scavenging activity and antioxidative capacity when compared with the antioxidant activity of 82 pure substances, among which 1 mM of vitamins C and B9 have shown the highest TEAC values as performed with the DPPH assay (267 µM and 230 µM, respectively) [61]. In this sense, it would be a reasonable idea to express the antioxidant activity (strength) of hydrolates as milli-or micromoles of Trolox equivalents per L of hydrolate instead of the various [62,63] and somewhat confusing [64] formats found in the literature.…”

Section: Antioxidative Properties Total Phenolics and Reducing Sugar ...mentioning

confidence: 99%

Multistep Approach Points to Compounds Responsible for the Biological Activity and Safety of Hydrolates from Nine Lamiaceae Medicinal Plants on Human Skin Fibroblasts

Smiljanić,

Prodić,

Trifunovic

et al. 2023

Antioxidants

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As byproducts of essential oil distillation, hydrolates are used in natural cosmetics/biomedicine due to their beneficial skin effects. However, data on their safety with relevant biological targets, such as human skin cells, are scarce. Therefore, we have tested nine hydrolates from the Lamiaceae family with skin fibroblasts that are responsible for extracellular collagenous matrix builds. Thyme, oregano, and winter savoury hydrolates showed several times higher total phenolics, which correlated strongly with their radical scavenging and antioxidative capacity; there was no correlation between their viability profiles and the reducing sugar levels. No proteins/peptides were detected. All hydrolates appeared safe for prolonged skin exposure except for 10-fold diluted lavender, which showed cytotoxicity (~20%), as well as rosemary and lavandin (~10%) using viability, DNA synthesis, and cell count testing. Clary sage, oregano, lemon balm, and thyme hydrolates (10-fold diluted) increased fibroblast viability and/or proliferation by 10–30% compared with the control, while their viability remained unaffected by Mentha and winter savoury. In line with the STITCH database, increased viability could be attributed to thymol presence in oregano and thyme hydrolates in lemon balm, which is most likely attributable to neral and geranial. The proliferative effect of clary sage could be supported by alpha-terpineol, not linalool. The major volatile organic compounds (VOCs) associated with cytotoxic effects on fibroblasts were borneol, 1,8-cineole, and terpinene-4-ol. Further research with pure compounds is warranted to confirm the roles of VOCs in the observed effects that are relevant to cosmetic and wound healing aspects.

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QSAR Regression Models for Predicting HMG-CoA Reductase Inhibition

Ancuceanu,

Popovici,

Drăgănescu

et al. 2024

Pharmaceuticals

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Background/Objectives: HMG-CoA reductase is an enzyme that regulates the initial stage of cholesterol synthesis, and its inhibitors are widely used in the treatment of cardiovascular diseases. Methods: We have created a set of quantitative structure-activity relationship (QSAR) models for human HMG-CoA reductase inhibitors using nested cross-validation as the primary validation method. To develop the QSAR models, we employed various machine learning regression algorithms, feature selection methods, and fingerprints or descriptor datasets. Results: We built and evaluated a total of 300 models, selecting 21 that demonstrated good performance (coefficient of determination, R2 ≥ 0.70 or concordance correlation coefficient, CCC ≥ 0.85). Six of these top-performing models met both performance criteria and were used to construct five ensemble models. We identified the descriptors most important in explaining HMG-CoA inhibition for each of the six best-performing models. We used the top models to search through over 220,000 chemical compounds from a large database (ZINC 15) for potential new inhibitors. Only a small fraction (237 out of approximately 220,000 compounds) had reliable predictions with mean pIC50 values ≥ 8 (IC50 values ≤ 10 nM). Our svm-based ensemble model predicted IC50 values < 10 nM for roughly 0.08% of the screened compounds. We have also illustrated the potential applications of these QSAR models in understanding the cholesterol-lowering activities of herbal extracts, such as those reported for an extract prepared from the Iris × germanica rhizome. Conclusions: Our QSAR models can accurately predict human HMG-CoA reductase inhibitors, having the potential to accelerate the discovery of novel cholesterol-lowering agents and may also be applied to understand the mechanisms underlying the reported cholesterol-lowering activities of herbal extracts.

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Antioxidant Activity of Pharmaceuticals: Predictive QSAR Modeling for Potential Therapeutic Strategy

Cited by 4 publications

References 27 publications

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

In vitro and in vivo assessment of the antioxidant potential of isoxazole derivatives

Multistep Approach Points to Compounds Responsible for the Biological Activity and Safety of Hydrolates from Nine Lamiaceae Medicinal Plants on Human Skin Fibroblasts

QSAR Regression Models for Predicting HMG-CoA Reductase Inhibition

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