Olanexidine

In July 2015, olanexidine gluconate, a biguanide compound with remarkable antibacterial activity, was approved by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan for skin antisepsis at surgical sites. The drug was developed and marketed by Otsuka Pharmaceutical in Japan and is available as topical solution (1.5%). Olanexidine gluconate exhibited efficacy against a wide range of bacterial strains, especially Grampositive bacteria. In vitro experiments exploring its mechanism of action indicated that olanexidine interacts with bacterial surface molecules (such as lipopolysaccharides and lipoteichoic acid), disrupting the cell membranes of liposomes. These models suggest that the drug permeates the membranes of both Escherichia coli and Staphylococcus aureus and denatures proteins at relatively high concentrations (>160 g/mL).

Olanexidine is an antibacterial agent. Olanexidine is active against a wide range of bacteria, imcluding both Gram-positive and Gram-negative bacteria Olanexidine is also an antiseptic. Olanexidine can be used in the research of infection and inflammation[1][2][3].

ChEBI: Olanexidine is a dichlorobenzene.

The synthesis of olanexidine gluconate is relatively straightforward, involving the linkage of an n-octyl side chain and a dichlorobenzylamine through a bis-guanidyl lynchpin. The synthesis began with the reaction of commercial noctylamine (17) with sodium dicyanamide in the presence of concentrated sulfuric acid in refluxing n-butyl acetate to give rise to 1-cyano-3-octylguanidine (18) in 86% yield . Conditions employed to subsequently secure biguanidine 20 as the HCl salt hemihydrate in 77% yield were nearly identical to those used for the conversion of 17 to 18. Finally, treatment of 20 with sodium hydroxide in the presence of gluconic acid (21) gave rise to olanexidin gluconate (II) in almost quantitative yield.

[1] Hagi A, et al. Bactericidal Effects and Mechanism of Action of Olanexidine Gluconate, a New Antiseptic. Antimicrob Agents Chemother. 2015 Aug;59(8):4551-9. DOI:10.1128/AAC.05048-14
[2] Nii T, Yumoto H, Hirota K, Miyake Y. Anti-inflammatory effects of olanexidine gluconate on oral epithelial cells. BMC Oral Health. 2019 Nov 8;19(1):239. DOI:10.1186/s12903-019-0932-0
[3] Imai K, et al. Disinfection efficacy and mechanism of olanexidine gluconate against norovirus. Am J Infect Control. 2022 Jul;50(7):764-771. DOI:10.1016/j.ajic.2021.11.020
[4] Nakata H, et al. Effects of olanexidine gluconate on preoperative skin preparation: an experimental study in cynomolgus monkeys. J Med Microbiol. 2017 May;66(5):678-685. DOI:10.1099/jmm.0.000462