Recent Development of Benzotriazole-based Medicinal Drugs

Azole heterocyclic compounds exhibit wide range of medicinal applications in the treatment of various types of diseases [1]. Especially, triazole derivatives as medicinal drugs have been playing important roles in medicinal chemistry [2-4], and a lot of triazole analogs including imidazole [5], thiazole [6], carbazole [7,8], oxazole [9] and benzimidazole [10,11], etc. have also been found to be widely used in clinic. Benzotriazole is a fused aromatic nitrogen heterocycle of benzene ring with triazole, and its derivatives have been paid increasingly special attention due to their widely potential applications as medicinal drugs [12], corrosion inhibitors [13], man-made materials [14], supramolecular ligands [15], therefore large numbers of researches have already been focused on this attractive area. Notably, bioactive benzotriazole-based compounds are being deeply exploited all over the world to treat different kinds of puzzling diseases like cancers and the current researches of benzotriazole derivatives in medicinal chemistry have achieved great progress. Different from triazole, the fused benzene ring makes benzotriazole nucleus possess a larger conjugated system to form π-π stacking interactions, and its three nitrogen atoms make it easy to form hydrogen bonds and coordination bonds, thereby benzotriazole derivatives are more ready to bind with a variety of enzymes and receptors in biological system via diverse non-covalent interactions, resulting in a broad spectrum of biological activities. Furthermore, benzotriazole compounds could bind with different metal ions to produce benzotriazole-containing metal complexes, which may possess the bioactivities of both benzotriazole derivatives themselves and supramolecular agents, thus possibly exerting double action mechanisms to overcome drug resistances [16]. For the above reasons, benzotriazole moiety has been commonly employed to construct innovative drug molecules [17]. Particularly, some anticancer benzotriazole derivatives such as vorozole and TBB have been in clinical use or trial. Recently, more and more benzotriazole derivatives with effective pharmacological properties, low toxicity, few side effects, little multi-drug resistance, good water solubility, promising bioavailability, diversity of drug administration as well as broad bioactive spectrum have been frequently discovered, which have shown large development value and potentiality as medicinal drugs [18]. In view of these, on the basis of authors’ researches and other literature in recent five years, this work for the first time systematically reviewed the progress of benzotriazole compounds in medicinal chemistry, including as anticancer, antifungal, antibacterial, antitubercular, antiviral, antiparasitic, antioxidative, as well as other medicinal drugs, and some comments on structure-activity relationships are also discussed.