Our research within the field of azaheterocycles derivatives with antimicrobial activity (antibacterial, antifungal, antituberculosis) was started in the early ’90-th and, since than until today we bring important contributions in the field in terms of new classes and new compounds with significant antimicrobial activity. We synthetize hundreds of new azaheterocycles and we develop new setup procedures for their synthesis, these including eco-friendly methods using MW and US technology. Therefore, based upon our aforementioned expertise, within this project we will bring new contributions to the field of antimicrobial therapy and green chemistry, aiming to obtain new classes of antimicrobial derivatives and to develop new setup procedures for synthesis of azaheterocycles, eco-friendly including. In order to obtain our new hybrid classes of antimicrobials we use molecular hybridization approach, by the combination of two or more bioactive scaffolds with synergistic improvement in the biological activity. According with the literature data, the hybrid molecule is supposed to be more active than its parent fragments. As far for eco-friendly setup procedures we will use MW and US technology. The concrete objectives of the project and the elements of originality and innovation of this project consist in:
O1. To design and synthetise new hybrid azaheterocycles derivatives (type Q1, Q2) having in the same molecule an azine (Π–deficient) heterocycle, one or two (Π–rich) imidazole/benzimidazole heterocycle, via diverse aliphatic linker/spacers.
O2. To design and synthetise new hybrid azaheterocycles derivatives (type Q3 to Q7) having in the same molecule one, two or three azine (Π–deficient) heterocycle, one or two triazole (Π–rich) molecule, and diverse aliphatic and/or aromatic linker/spacers.
O3. To design and synthetise new hybrid azaheterocycles derivatives (type Q8, Q9, Q10) having in the same molecule a Π–deficient diazine heterocycle (pyridazine, phthalazine,bis-pyridazine) and triazole (Π–rich) molecule, anchored with diverse substituent’s, including anthracene fluorophore
O4. To design and synthetise new hybrid azaheterocycles derivatives (type Q11, Q12) having in the same molecule bis-pyridazine and azine (Π–deficient), and a triazole (Π–rich) molecule, anchored with diverse substituent’s.
O5. To design and synthetize new hybrid azaheterocycles derivatives (Q13) having in the same molecule an acetophenone unit, two azine and two triazole heterocycles.
O6. To design and synthetize new hybrid azaheterocycles derivatives (Q14, Q15) having in the same molecule an acetophenone unit, two azine and two imidazole and/or oxazole heterocycles.
O7. Synthesis of supramolecular host-guest assembly based of β-cyclodextrins and azaheterocycles as drug delivery systems.
O8. Evaluation of the antimicrobial and antifungal activity, investigation of the mechanism of actions of antimicrobials, performing SAR correlations, studies the drug delivery of β-cyclodextrin /azaheterocycle inclusion complexes.
O9. To elaborate new experimental setup procedure for nitrogen derivatives, and/or to adapt the existing one, particularly environmentally friendly methods, using MW and/or US technology.
O10. Increasing the research skills and abilities of the young Ph-D and master students. O11. Increasing the visibility of Romanian science through publication in prestigious ISI journals. O12. To establish new collaboration relationship with partners from inside and outside of Romania that are working in academia, pharmaceutical industry and related fields.