Petru Poni

SEFTAA

The synthesis and evaluation of some tribenzotriquinacene-flavonoids tripodal antibacterial agents

Petru Poni

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Summary:

Since their discovery, the overuse of antibiotics in both medicine and agriculture has paved the way to the emergence of drug resistant bacteria, which in turn gave rise to an ever-increasing demand for new, more effective antibiotics. Many of the recently developed drugs, however, were built on the same molecular scaffolds as older antibiotics, that various bacteria have developed resistance to. For instance, the second, third and fourth generation cefalosporins were each developed as microorganisms became resistant to the previous generation. The development of antibiotics based on new molecular scaffolds, that are able to bypass the various resistance mechanisms employed by drug resistant bacteria, is becoming more urgent with each passing day. Flavonoids are a diverse class of plant polyphenols that exhibit a wide range of biological activities. Amongst these, several flavonoids were found to display antibacterial properties. Moreover, flavonoids have also been shown to have a synergistic effect when administered with other antimicrobial agents against drug resistant bacteria. This makes flavonoids promising candidates in the ongoing search for new antibacterial drugs.

The project leader previously worked on a class of tricyclic flavonoids bearing a 1,3-dithiolium ring that displayed strong antimicrobial properties. By grafting these to a tribenzotriquinacene unit, this project aims to synthesize a new class of tripodal antibacterial agents. Once synthesized, these derivatives will be tested against various lines of bacteria, their structure will be optimized and preliminary cytotoxicity tests will be performed.

Successful implementation of this project should deliver effective antimicrobial agents based on a new molecular scaffold, with the potential of limiting the loss of human lives and reducing treatment time and costs.

Objectives:

1. The synthesis of the tripodal antibacterial agents and their structural characterization (elemental analysis, NMR, MS, IR, UV-vis).

2. Evaluation of the antibacterial potential and mechanism of action of the newly synthesized TBTQ-flavonoids hybrids.

3. Conducting a structure-activity study concerning the antibacterial properties of the newly synthesized compounds.

4. Cytotoxicity tests for the derivatives with the optimized structure, should their antibacterial properties prove to be promising.