BrainMap

Mr. Mihail Lucian Birsa

Prof. dr. habil.

Prof. dr. habil. - UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Researcher | Teaching staff | Scientific reviewer | PhD supervisor

Web of Science ResearcherID: C-1568-2012

Curriculum Vitae (04/07/2024)

Expertise & keywords

Tricyclic 1,3-dithiolium flavonoids - New weapons to combat antibiotic resistance Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2019-2235 2020 - 2022

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://cercetare.bio.uaic.ro/grupuri/bioactive/content/grants/ped2020.html

Abstract:

Increasing resistance of microbial pathogens against many available antibiotics is a medical problem of major concern all over the world. Antimicrobial resistance (AMR) poses a serious global threat due to the emergence, spread and persistence of multidrug resistant (MDR) bacteria or 'superbugs' such as the notorious Staphylococcus aureus. The discovery of new and more efficient antimicrobial drugs is therefore a matter of high priority among scientists and clinicians worldwide. A potential solution could be represented by tricyclic 1,3-dithiolium flavonoids with a bromine substituent at the benzopyran core (TSBrFls), a group of compounds with completely new structures, unrelated to any known natural compound, synthetized by our research group. The preliminary results showed that one particular TSBrFl - 4b displayed very potent antibacterial properties with low minimum inhibitory concentrations (0.24 μg/ml against S. aureus and 3.9 μg/ml against E. coli). The inhibitory effect was stronger compared to many antibiotics (gentamicin, ampicillin, kanamycin), natural or other synthetic flavonoids reported in literature. Moreover, a synergistic interaction with penicillin and fluconazole was recorded. The present proposal aims to validate TSBrFls as a new class of antimicrobial agents to be used against MDR strains. Further studies are necessary in order to: synthetize three new TSBrFls; optimize the synthesis procedure; test TSBrFls against a broader spectrum of MDR strains (including Candida sp.); evaluate the mode of action in relation with some important microbial resistance and virulence factors; assess shelf-life, solubility and cytotoxicity. The results obtained after the full implementation of the current proposal will allow us to move from the preliminary tests and experimental proof of concept (TRL3) to the validation of TSBrFls as new efficient antimicrobial agents (TRL4).

NEW SYNTHETIC FLAVONOIDS WITH ANTIMICROBIAL APPLICATIONS Call name: P 3 - SP 3.1 - Proiecte de mobilități, România-Franța (bilaterale)
PN-III-P3-3.1-PM-RO-FR-2019-0102 2019 - 2021

Role in this project: Key expert

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); Université de Lille (FR)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.bio.uaic.ro/cercetare/grupuri/bioactive/content/grants/ro-fr2019.html

Abstract:

One of the most serious global threats of this century is the emergence and spread of antimicrobial-resistant pathogens. In agriculture, phytopathogenic microorganisms such as Fusarium, Botris or Zymoseptoria represent a major threat to both agricultural production and ecosystems stability. In the medical field, Candida species are responsible for over 64% of fungal infections, with a mortality rate of 40%. Therefore, finding new classes of more effective antimycotic drugs is a matter of maximum priority. In this context, this project proposes the development of a new class of antifungal products, represented by tricyclic flavonoids with different halogens as substituents at the benzopyran core. Preliminary results have shown that these flavonoids have important bacteriostatic and bactericidal properties. Additional studies, using the French partner's antifungal molecules experience, are needed to expand the antimicrobial spectrum of synthetic flavonoids. Also, collaboration will allow us to understand the mechanisms of action and to acquire knowledge on cytotoxicity. At the end of the project we will be able to propose a new high-efficiency antimycotic product, thus contributing to the strengthening of the scientific relationship between our laboratory and Lille University, France.

The synthesis of new hybrid [2.2]paracyclophane-flavonoids systems with potential antimicrobial activity Call name: P 1 - SP 1.1 - Proiecte de cercetare Postdoctorală
PN-III-P1-1.1-PD-2016-0962 2018 - 2020

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.chem.uaic.ro/files/File/proiect-sarbu/contact.html

Abstract:

A major problem in our modern-day society, especially in the medicine field, is represented by drug-resistant microbes, which are resistant to a more and more broad spectrum of antibiotics. This issue is due to the extensive, sometimes negligent use of antibiotics in human treatment and agriculture. Therefore, the synthesis of new and more active antibiotics, preferably based on new molecular scaffolds, are is needed. In this context, flavonoids represent potentially good candidates for such antimicrobial agents.

Flavonoids are a class of polyphenolic compounds that act as secondary metabolites in plants and possess a C6-C3-C6 backbone. Presently, more than 9000 flavonoids are known, with this number increasing every year. The great interest for this class of compounds derives from the wide display of biological activities, which are in a strong relationship with the structure of the flavonoids. It is to be mentioned that for centuries, mixtures that contain flavonoids have been used in traditional medicine for treatment and prevention of various infectious and toxin-mediated diseases, such as wound infections, acne, respiratory infection, gastrointestinal disease and urinary tract infections.

The other class of compounds, that we are trying to merge with the flavonoid framework, is represented by [2.2]paracyclophanes. Cyclophanes are strained organic molecules which contain aromatic ring(s) as well as aliphatic unit(s). The aromatic rings provide rigidity to their structure, whereas the aliphatic unit(s) forms bridge(s) between the aromatic rings and also provide flexibility to the overall structure.

The main target of the present project is to synthesize new hybrid [2.2]paracyclophane-flavonoids systems with potential antimicrobial activity. The introduction of one or more tricyclic flavonoids moieties into the [2.2]paracyclophane framework is worth investigating, as the new derivatives might display enhanced antimicrobial activity.

1,3-Dithiolium Flavonoids With Antimicrobial Activities Call name: P 2 - SP 2.1 - Proiect experimental - demonstrativ
PN-III-P2-2.1-PED-2016-1817 2017 - 2018

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.chem.uaic.ro/files/File/2017-2018/cercetare/proiect-prof-birsa/152-ped-birsa.pdf

Abstract:

The antibacterial properties of a new class of synthetic 1,3-dithiolium flavonoids is investigated in order to disclose new antibacterial drugs, disinfectants or antiseptics products. The objectives of this study are the following:

1. Optimization of 1,3-dithiolium flavonoids synthesis and evaluation of their structural stability. Synthetic optimization targets a one-pot synthesis and a large scale procedure, necessary steps in order to prepare a strategy for a technological transfer. Investigations of the tricyclic flavonoids stability in solutions or in solid state under various conditions will be performed before beginning the antimicrobial or cytotoxicity tests.

2. Preparation and morphology optimization of biocompatible polymeric membranes for controlled release of flavonoides potential drugs using transdermal patches. In order to achieve this objective we intend to use biocompatible polymers and prepare membranes loaded with the flavonoides suitable for controlled drug delivery.

3. To test the antimicrobial properties and understand the mechanism of action. The susceptibility of a wide range of bacteria to 1,3-dithiolium flavonoids will be assessed in relation with reference antibiotics; MIC/MBC values will be determined for future practical applications.

4. To investigated the cytotoxicity effects of the 1,3-dithiolium flavonoids. The output of this objective will guide us through an opinion about the potential use of these compounds as new antibacterial drugs/disinfectants/antiseptics.

5. Comparative analysis of the results for laboratory validation of the best candidate as antibacterial agent

6. Preparation of a patent applications

The study of the effect of organic complexing agents of Fe(III) or Fe(II) on iron monosulfide oxidative dissolution Call name: Joint Applied Research Projects - PCCA-2011 call, Type 1
PN-II-PT-PCCA-2011-3.1-0683 2012 - 2016

Role in this project:

Coordinating institution: UNIVERSITATEA DIN CRAIOVA

Project partners: UNIVERSITATEA DIN CRAIOVA (RO); UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO); INSTITUTUL NATIONAL DE CERCETARE - DEZVOLTARE PENTRU FIZICA MATERIALELOR BUCURESTI RA (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website: http://www.chem.uaic.ro/files/file/ecafe/index.html

Abstract:

The iron monosulfides (FeS) oxidative dissolution is a process that produces various environmental problems. Although the dissolved oxygen is the final acceptor of the electrons (and most common oxidant in natural environments), the actual species that takes electrons from mineral sulfides is ferric iron (Fe(III)). Accordingly, the control of Fe(III) concentration can suppress the oxidation of FeS. A study in quasi-environmental conditions, in the presence of Fe(III) or Fe(II) (ferrous iron, the species that generates Fe(III) in the presence of oxygen) complexing agents (ligands), can lead at a better understanding of FeS oxidative dissolution process, as well as at the proposal of adequate strategies for its suppression. Taking into account the importance and complexity of this subject, the study that will be realized is focused on two directions: a theoretical direction of fixing of the main aspects of FeS oxidative dissolution and, respectively, a practical direction, materialized by experimental studies, having as objectives achievement of our own results and their interpretation regarding to literature data. The main purposes of this study are the accurate characterization of FeS oxidative dissolution process in presence of Fe(III) and Fe(II) complexing agents, determining the temporal evolution of some indicators of FeS oxidation degree (pH, Eh, total iron concentration, total dissolved sulfur concentration, corrosion current densities, polarization resistances, etc.), surface analysis of reacted mineral samples by X-ray diffraction (XRD), FTIR spectroscopy, Raman spectroscopy, Atomic Force Microscopy, Scanning Electron Microscopy and the selection of ligands having an adequate inhibition efficiency of FeS oxidative dissolution, in order to create effective strategies of the suppression of the environmental contamination.

4th European Organic Chemistry Congress Call name: P 1 - SP 1.1 - Proiecte de mobilitate pentru cercetatori
PN-III-P1-1.1-MC-2017-1629 2017 -

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website:

Abstract:

Call name: Premierea obtinerii atestatului de abilitare - Competitia 2015
PN-II-RU-ABIL-2015-2-0175 2015 -

Role in this project:

Coordinating institution: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI

Project partners: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Affiliation: UNIVERSITATEA "ALEXANDRU IOAN CUZA" IASI (RO)

Project website:

Abstract:

FILE DESCRIPTION	DOCUMENT
List of research grants as project coordinator	Download (6.21 kb) 31/03/2017
List of research grants as partner team leader	Download (10.92 kb) 02/04/2015
List of research grants as project coordinator or partner team leader
Significant R&D projects for enterprises, as project manager
R&D activities in enterprises
Peer-review activity for international programs/projects