Identification, synthesis and biological activity of alkyl-guanidine oligomers as potent antibacterial agents

Abstract

In the last two decades, the repertoire of clinically effective antibacterials is shrinking due to the rapidly increasing of multi-drug-resistant pathogenic bacteria. New chemical classes with innovative mode of action are required to prevent a return to the pre-antibiotic era. We have recently reported the identification of a series of linear guanidine derivatives and their antibacterial properties. A batch of a promising candidate for optimization studies (compound 1) turned out to be a mixture containing two unknown species with a better biological activity than the pure compound. This serendipitous discovery led us to investigate the chemical nature of the unknown components of the mixture. Through MS analysis coupled with design and synthesis we found that the components were spontaneously generated oligomers of the original compound. Preliminary biological evaluations eventually confirmed the broad-spectrum antibacterial activity of this new family of molecules. Interestingly the symmetric dimeric derivative (2) exhibited the best profile and it was selected as lead compound for further studies.

Focused library of phenyl-fused macrocyclic amidinoureas as antifungal agents

“…Aldehydes 6a-f were first converted into aldoximes 7a-f and then reduced to benzyl amines 8a-f via zinc-mediated hydrogenation. Derivatives 9a-f were finally achieved by guanylating the primary amine moiety with N,N'-Di-Boc-1H-pyrazole-1-carboxamidine [26,27]. The primary amine belonging to the previously described linker 10 [20] was reacted with the diBoc-guanidino moiety of 9a-f, furnishing tert-butoxycarbonyl (Boc)-protected amidinoureas 11a-f [28].…”

In Vitro and In Vivo Evaluation of the Toxic Effects of Dodecylguanidine Hydrochloride

“…Cationic active biocides, such as quaternary ammonium compounds (QACs), guanidine derivatives, and amphoteric surfactants, have been widely used for a long time. Many biocides use high binding affinity with a containing cationic group to capture negatively charged bacteria, resulting in disruption of their membrane [41][42][43][44]. Having a highly positively charged part is the typical chemical characteristic of guanidine-based chemicals, and it is well known that positively charged parts of chemicals can penetrate the cell membrane easily, inducing systemic toxicity in vivo [45][46][47].…”

Antimicrobial two-dimensional covalent organic nanosheets (2D-CONs) for the fast and highly efficient capture and recovery of phosphate ions from water

“…12,13 Guanidine easily gets protonated (guanidinium), even at physiological pH (p K a 12.3), which could induce the self-exfoliation of CONs, leading to their direct applications without the need for additional post-synthetic alterations. 12,14,15 In this regard, we rationally designed and synthesized porous and self-exfoliative pyrene-based guanidine-containing covalent organic nanosheets (gCONs) to remove and recover oxoanions, like phosphate, from the aqueous system. Although various polymeric materials have already been developed to remove and recover phosphate ions, aqueous insolubility augments the use of gCONs in heterogeneous water-resistant environments.…”