Synthesis and In Vitro Antimicrobial SAR of Benzyl and Phenyl Guanidine and Aminoguanidine Hydrazone Derivatives.

Content Provider	Europe PMC
Author	Dohle, Wolfgang Su, Xiangdong Nigam, Yamni Dudley, Edward Potter, Barry V. L.
Editor	Muñoz-Torrero, Diego Osborn, Helen Doerksen, Robert J.
Copyright Year	2022
Abstract	A series of benzyl, phenyl guanidine, and aminoguandine hydrazone derivatives was designed and in vitro antibacterial activities against two different bacterial strains (Staphylococcus aureus and Escherichia coli) were determined. Several compounds showed potent inhibitory activity against the bacterial strains evaluated, with minimal inhibitory concentration (MIC) values in the low µg/mL range. Of all guanidine derivatives, 3-[2-chloro-3-(trifluoromethyl)]-benzyloxy derivative 9m showed the best potency with MICs of 0.5 µg/mL (S. aureus) and 1 µg/mL (E. coli), respectively. Several aminoguanidine hydrazone derivatives also showed good overall activity. Compounds 10a, 10j, and 10r-s displayed MICs of 4 µg/mL against both S. aureus and E. coli. In the aminoguanidine hydrazone series, 3-(4-trifluoromethyl)-benzyloxy derivative 10d showed the best potency against S. aureus (MIC 1 µg/mL) but was far less active against E. coli (MIC 16 µg/mL). Compound 9m and the para-substituted derivative 9v also showed promising results against two strains of methicillin-resistant Staphylococcus aureus (MRSA). These results provide new and potent structural leads for further antibiotic optimisation strategies.
Journal	Molecules
Volume Number	28
DOI	10.3390/molecules28010005
PubMed Central reference number	PMC9822361
Issue Number	1
PubMed reference number	36615201
e-ISSN	14203049
Language	English
Publisher	Molecular Diversity Preservation International (MDPI)
Publisher Date	2022-12-20
Access Restriction	Open
Subject Keyword	benzyl guanidine benzyl aminoguanidine hydrazone guanylation antimicrobial activity methicillin-resistant Staphylococcus aureus (MRSA)
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry Medicine Chemistry Drug Discovery Pharmaceutical Science Analytical Chemistry Molecular Medicine Organic Chemistry