Benzimidazole - based small molecules targeting resistant Escherichia coli infections

Summary

Antimicrobial resistance is an imminent threat worldwide, therefore, the need for the development of new classes of antibiotics is greater than ever. One of the urgent microbial threats is Escherichia coli infections. With major resistance to fluoroquinolones and colistin, development of new antibacterial agents to target E. coli infections is of utmost importance.

Using phenotypic screening, we tested a series of benzimidazole-based derivatives against several gram-negative bacteria. A promising lead (EC-9) was identified against E. coli (TolC mutant strain) with MIC value of 2 µg/ml. EC-9 showed synergistic activity when combined with colistin against E. coli (wild type strains). Based on these premises, EC-9 was used as a lead compound for the development of novel antimicrobial agents against E. coli infections.

Achievements

• Rational optimization of the phenotypic hit and SAR summary for benzimidazole derivatives.
• Ligand-based analysis of active small molecules and election of optimized hits.
• Purchase Chemicals and Solvents.
• Starting in synthesis of intermediatesand and final compounds of scheme 1.
• The intermediates and 18 final compounds were synthesized.
• All the synthesized intermediates and final compounds were purified using column chromatography (DCM/MeOH) to yield the desired final products and the chemical structures were elucidated by 1H NMR.

• Compounds were already sent to USA to carry out the biological tests in collaboration with Prof. Mohamed Seleem at Purdue University, USA.

List of Publications from the Project

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Partners

Project Members

• Eman Mahmoud Elawady Dokia
• Sandra Nabil Morad

Project Leaders

• Mai Adel Mohamed