Imidazole and Pyrazole: Privileged Scaffolds for Anti-Infective Activity

Heterocyclic scaffolds like imidazole and pyrazole are attractive options to medicinal and synthetic chemists for the development of drugs. Nature utilizes the unique type of imidazole ring in numerous biological molecules such as histamine, vitamin B12, deoxyribonucleic acid (DNA) and haemoglobin for exerting various biological functions. This shows that the imidazole ring is vital to many physiological processes and hence important for modulating altered physiology. Imidazole and pyrazole analogues have been reported to show a varied spectrum of activities like antibacterial, antifungal, antiviral, antimalarial, antitubercular, antileishmanial, anticancer, anti-inflammatory, antineuropathic, antiparasitic, antihistaminic, antihypertensive, antiobesity, etc. and hence are valuable scaffolds for the development of new therapeutic agents. Many azole-based antibacterial and antifungal agents have been extensively studied as drug candidates and some of them are used clinically for instance ketoconazole, itraconazole, fluconazole, posaconazole and voriconazole, which suggests their great development value. Myriad of structural modifications on these scaffolds have provided a wide spectrum of activity and scope for the enhancement of activity. Reviews on the biological importance of these scaffolds have been published over the past decade or two. However, we did not come across reviews that combined the synthetic strategies of some bioactive substituted imidazole and pyrazole compounds along with the impact of substitutions on their anti-infective activity. The pursuit of structurally novel anti-infective imidazoles and pyrazoles with increased potency, broader spectrum and lower toxicity is a highly challenging task and is of great interest in medicinal chemistry. This review will be useful for synthesizing imidazole and pyrazole analogues for the development of new potent anti-infective agents that will also help overcome the issue of emerging multidrug resistance observed with the existing anti-infective drugs.