Bactericidal effect of HM-242, a novel disinfectant, against Pseudomonas aeruginosa.

The bactericidal effect of HM-242, a novel antimicrobial agent, against Pseudomonas aeruginosa was investigated by using Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) values and the time-kill study. Furthermore, we also morphologically investigated its effect against P. aeruginosa by use of transmission electron microscopy (TEM) in comparison with that of chlorhexidine digluconate (CHG). The bactericidal activity of HM-242 after 1 min incubation evaluated by MBC was 25 microg/mL, while the MBC of CHG was 50 microg/mL. In the time-kill study, the killing activity of HM-242 with 25 microg/mL incubation was stronger than that of CHG with 50 microg/mL incubation. MIC values of HM-242 and CHG against P. aeruginosa were 25 microg/mL and 12.5 microg/mL, respectively. We also observed via TEM the morphological changes in the test bacteria after being treated with each drug at 1/2MBC, 1MBC, 2MBC and 4MBC after 1 min or 5 min incubation. Under treatment with the same concentration of the test drugs, the cell damage with HM-242 treatment was greater than that with CHG. The appearance of empty cells was recognized at the concentrations greater than 50 microg/mL (2MBC) of HM-242 and 200 microg/mL of CHG (4MBC) after 1 min exposure, although no cell damage was evident below these concentrations. The cell-damaging effect against the test strain was dependent on the drug concentration and incubation time. The release of cell components and bleb formation were also recognized. These results suggest that HM-242 has more potent bactericidal activity in low concentrations under shorter time treatments than CHG. Both HM-242 and CHG act on the cell membrane and cell wall of P. aeruginosa and can destroy the cell integrity. We finally emphasize that HM-242 as well as CHG might be a suitable disinfectant for use in the medical field.

In vitro evaluation of the antimicrobial activity of HM-242, a novel antiseptic compound.

The antimicrobial activities of N(4)-octyl-6,6-dimethyl-N(2)-(4-methylbenzyl)-1,6-dihydro-1,3,5-triazine-2,4-diamine (HM-242), a novel synthetic compound, were compared with those of chlorhexidine gluconate (CHG). HM-242 was a more potent microbicide than CHG in vitro; however, its minimal inhibitory concentrations were similar. In particular, HM-242 killed various Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecalis, both efficiently and rapidly. HM-242 also showed potent virucidal activity against enveloped viruses such as influenza virus and herpes simplex virus. These characteristics suggest that HM-242 may well be useful as an antiseptic.

Synthesis of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivatives as topical antiseptic agents.

A series of novel 4,6-di(substituted)amino-1,2-dihydro-1,3,5-triazine derivatives designed to have ClogP of 5.1-7.5 was synthesized and evaluated for their antiseptic properties by MIC and MBC tests against Gram-positive and Gram-negative bacteria, including MRSA, VRE, and P. aeruginosa. Among these compounds, 4-alkyl-6-aralkyl derivatives having ClogP of 6.6-7.1 and 4-alkyl-6-aryl or 4,6-dialkyl derivatives with ClogP of 6.0-6.4 showed pronounced antibacterial activities in both tests.