Biguanide derivatives as surfactants and antimicrobial agents for pharmaceutical applications

Biguanide is an interesting molecule whose chemical moiety can be found in the structure of several compounds with different therapeutic activities such as antidiabetic, antiviral, antimalarial, antibacterial, antimycotic, anti-HIV. Biguanide derivatives are currently employed in clinics as orally-administered hypoglycemic agents and they have been also proposed for the treatment of several other conditions (e.g. polycystic ovary syndrome, cancer, tubercolosis) [1]. Regarding the antimicrobial activity, several biguanide derivatives are known to be active against a wide range of gram positive and gram negative bacteria as well as fungi, yeasts, viruses [Ref]. Indeed, a cationic bisbiguanide as chlorhexidine (and its salt form chlorhexidine digluconate) is one of the most used topical disinfectant and antiseptic agent for skin and mucosa. Chemical research about the biguanide moiety led to the production of oligomers as polyhexamethylenebiguanide (PHMB), which consists of 7-10 biguanide moieties connected by a hexamethylene linker. It shows a broad range of antimicrobial activity and finds applications for different purposes (e.g. disinfectant, preservative, biocide). Despite the large interest toward biguanides derivatives, no detailed studies have been conducted for the development of novel surface-active molecules bearing this chemical moiety. Indeed, only one study can be found in the literature in which a biguanide was linked to alkyl chains of a different length to produce amphiphilic molecules [3]. According to these premises, the biguanide moiety can be exploited to design new surfactants with a dual activity as surface-active molecules and antimicrobial agents. As such, in this work, a new series of amphiphilic compounds derived from the alkylation (C3, C6- and C10-) of 1-(orto-tolyl)biguanide was synthesized and characterized in terms of surface tension, aggregation properties and antibacterial activity.