diamidine

Diamidine is a term used to describe compounds that contain two amidine functional groups. Each amidine group has the structure RC(=NH)NH2, and in a diamidine the two amidine units are connected by a carbon-based linker, which may be aliphatic, aromatic, or heteroatom-containing. The two amidine groups render diamidines highly basic; at physiological pH they are typically doubly protonated, giving a dicationic species that strongly interacts with negatively charged biomolecules such as DNA and RNA and can cross membranes depending on substituents.

Diamidines are notable for medicinal use as antiparasitic and antimicrobial agents. Well-known examples include pentamidine, furamidine (DB75), diminazene aceturate (Berenil), and related compounds. They commonly act as DNA minor-groove binders, inhibiting replication and transcription in parasites, and some are used clinically to treat Pneumocystis jirovecii pneumonia, leishmaniasis, trypanosomiasis, or babesiosis, with use varying by region. Their selectivity and toxicity profiles are active areas of medicinal chemistry.

Chemistry and properties: Diamidines are usually prepared by linking two amidine-bearing fragments with a spacer; the length and nature of this spacer, as well as substituents on the amidine rings, strongly influence potency, selectivity, and pharmacokinetic properties. They are generally highly polar and cationic, which can limit oral bioavailability but promote uptake in certain parasites. Toxicity can be a concern, including nephrotoxicity and cardiotoxicity, and clinical use is often restricted to specific indications.