Projects / Programmes
Exploiting Known Natural Polyphenols as Potential New Therapeutics with Multiple Beneficial Health Effects
| Code |
Science |
Field |
Subfield |
| 4.03.05 |
Biotechnical sciences |
Plant production |
Phytomedicine |
| Code |
Science |
Field |
| 4.01 |
Agricultural and Veterinary Sciences |
Agriculture, Forestry and Fisheries |
natural polyphenols, antioxidants, anticarcinogenic activity, antimicrobial agents, quantum-mechanic simulations, biomolecular simulations, DPPH and ABTS assays, cyclic and differential pulse voltammetry, comet assay, MIC and MBC values, mechanistic studies, free radicals, chemical carcinogens
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
52709 |
PhD Jelena Tošović |
Chemistry |
Head |
2020 - 2022 |
50 |
Organisations (1)
Abstract
The need for novel drugs against well-known and novel diseases alike represents a never ending quest due to the ability of pathogens to adapt or find new ways of action. Due to their high abundance in human diet as well as impressive biological health functions polyphenols form excellent starting compounds for the development of new drugs. Among other activities, polyphenols exhibit promising antioxidative, anticancerogenic and antimicrobial functions. This fact is of exceptional importance for the proposed research project, as it will focus on the investigation of possible new therapeutics against oxidative stress related sicknesses and cancer, as well as on the designing of alternative prophylactic substances. The proposed research project will for the first time employ state-of-the-art computational and experimental techniques working hand in hand to investigate antioxidative, anticarcinogenic, and antimicrobial activities of three different classes of polyphenols. To identify polyphenols with the highest antioxidative potential spectrophotometric and electrochemical experiments will be used. Experimental results will be complemented with the quantum-mechanics based computational investigation of antioxidative mechanisms. For this purpose, reactions between polyphenols and physiological free radicals will be examined following the recently developed QM-ORSA methodology, which is based on thermodynamic and kinetic considerations of all possible mechanisms and reaction sites. To determine the most potent anticarcinogenic compounds among the investigated polyphenols cell gel electrophoresis (comet) assay will be utilized. Several computational methods will also be employed to gain a better insight into the anticarcinogenic mechanisms of investigated polyphenols. Novel and advanced computational method inverse molecular docking will be applied to discern polyphenols which inhibit protein targets involved in oncogenic signaling cascades. Moreover, using molecular dynamics simulations in connection with free energy calculations we will gain insights into molecular mechanisms and relative strengths of anticancerogenic activities of the studied polyphenols. An additional goal of the proposed research project forms a design of a standardized methodology for the investigation of anticarcinogenic action, Quantum-Mechanics test for Overall antiCarcinogenic activity (QMOCA), which will focus on the kinetic investigation of the reactions in which polyphenols act as scavengers of well-known chemical carcinogens. Developing of a standardized test for the overall anticarcinogenic activity would compare all the investigated polyphenols and discern the most potent scavengers of chemical carcinogens. Finally, in the light of growing antimicrobial resistance, we will identify new natural compounds with high antimicrobial potentials and measure the related minimum inhibitory (MIC) and minimum bactericidal (MBC) concentrations. Molecular mechanisms of antimicrobial activity will be investigated as well using the inverse molecular docking approach, whereas free energies and corresponding binding affinities between detected protein targets and polyphenolic ligands will be thoroughly studied using molecular dynamic simulation experiments. The ultimate goal of the proposed project is to find the most potent polyphenols or their mixtures, which after subsequent optimization can serve as functional food or feed supplements with high antioxidative, anticarcinogenic, and antimicrobial potentials. In addition, the combined experimental and theoretical studies will shed light on the intrigant molecular mechanisms which dictate the antioxidative, anticarcinogenic and antimicrobial features of the investigated polyphenols. Their understanding will disclose deeper relationships between structure and biological activities within and across different types of polyphenols for the first time.
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