Projects Cindro Group

Microorganisms as source of new antibiotics – From total synthesis to new chemical space and methodology (MicroSynTotal)

Antimicrobial resistance poses a significant problem in the global healthcare system. One solution is the development of new synthetic analogs of existing classes of antibiotics; however, bacteria can more easily modify their resistance mechanisms to such compounds. 

A longer-term solution to this problem lies in the development of new classes of antimicrobial compounds. As part of this project, representatives of three classes of compounds, previously isolated from natural sources, structurally characterized, and showing significant in vitro antimicrobial activity, especially against some resistant bacterial strains, will be synthesized for the first time. 

Antimicrobial testing will be conducted on the synthesized compounds to confirm their activity on a broader bacterial panel. The three classes of recently discovered compounds to be included in this project are:

  1. Enceleamycins
  2. Modified Cihunamides
  3. Callophycoic and Bromophycoic acids

 

During the development of synthetic approaches for individual classes of compounds, new synthetic methodology will also be developed for specific structural motifs of that class, aiming to develop a robust approach to problematic structural fragments. Some of the methodologies to be developed include double Grignard reactions based on the addition of various organometallic reagents to lactones and mechanochemical cyclization reactions of oligopeptides. Additionally, the synthesis of structural analogs in each of the mentioned groups is planned to enable SAR (Structure-Activity Relationship) studies on these classes of compounds.

IP-2024-05-5352

MicroSynTotal

Antimicrobial resistance represents a significant challenge in the global healthcare system. One potential solution is the development of new synthetic analogs of existing antibiotic classes. However, bacteria can more easily modify their resistance mechanisms against such compounds. A more sustainable solution to this problem lies in the development of new classes of antimicrobial compounds.

As part of this project, representatives of three classes of compounds will be synthesized for the first time. These compounds have previously been isolated from natural sources, structurally characterized, and shown to exhibit significant in vitro antimicrobial activity, particularly against some resistant bacterial strains. Antimicrobial testing will be conducted on the synthesized compounds to confirm their activity across a broader bacterial panel. The three recently discovered classes of compounds that will be addressed in this project are:

a) Penicyclones
b) Spiromastols and spiromastixones
c) Dispirolopyridines

During the development of synthetic approaches for these compound classes, new synthetic methodologies for specific structural motifs of each class will also be developed to establish a robust approach to challenging structural fragments. Some of the methodologies to be developed include the double Grignard reaction and nickel-catalyzed synthesis of diaryl ethers. Additionally, the synthesis of structural analogs within each of these classes is planned to facilitate SAR (Structure-Activity Relationship) studies of the respective compound classes.

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