A conjugate vaccine strategy that induces protective immunity against arecoline.

Betel-quid chewing addiction is the leading cause of oral submucous fibrosis and oral cancer, resulting in significant socio-economic burdens. Vaccination may serve as a promising potential remedy to mitigate the abuse and combat accidental overdose of betel nut. Hapten design is the crucial factor to the development of arecoline vaccine that determines the efficacy of a candidate vaccine. Herein, we reported that two kinds of novel arecoline-based haptens were synthesized and conjugated to Bovine Serum Albumin (BSA) to generate immunogens, which generated antibodies with high affinity for arecoline but reduced binding for guvacoline and no affinity for arecaidine or guvacine. Notably, vaccination with Arec-N-BSA, which via the N-position on the tetrahydropyridine ring (tertiary amine group), led to a higher antibody affinity compared to Arec-CONH-BSA, blunted analgesia and attenuated hypothermia for arecoline.

5-Formylsalicylic acid and 5-(benzimidazolium-2-yl)salicylate.

Both title compounds are derivatives of salicylic acid. 5-Formylsalicylic acid (systematic name: 5-formyl-2-hydroxybenzoic acid), C(8)H(6)O(4), possesses three good hydrogen-bond donors and/or acceptors coplanar with their attached benzene ring and abides very well by Etter's hydrogen-bond rules. Intermolecular O-H...O and some weak C-H...O hydrogen bonds link the molecules into a planar sheet. Reaction of this acid and o-phenylenediamine in refluxing ethanol produced in high yield the new zwitterionic compound 5-(benzimidazolium-2-yl)salicylate [systematic name: 5-(1H-benzimidazol-3-ium-2-yl)-2-hydroxybenzoate], C(14)H(10)N(2)O(3). Each imidazolium N-H group and its adjacent salicyl C-H group chelate one carboxylate O atom via hydrogen bonds, forming seven-membered rings. As a result of steric hindrance, the planes of the molecules within these pairs of hydrogen-bonded molecules are inclined to one another by ∼74°. There are also π-π stacking interactions between the parallel planes of the imidazole ring and the benzene ring of the salicyl component of the adjacent molecule on one side and the benzimidazolium component of the molecule on the other side.