Hybridization of Imidazole with Various Heterocycles in Targeting Cancer: A Decade's Work

Abstract

Cancer is the world‘s biggest global health concern. The prevalence and mortality rates of cancer remain high despite significant progress in cancer therapy. The search for more effective, as well as less toxic treatment methods for cancer, is at the focus of current studies. Approximately 24.6 million people are suffering from cancer across the world as per the world health organization (WHO). In the year 2020, approximately 10 million deaths were reported due to cancer which has emerged as the second leading cause of mortality across the globe. Anticancer medicines have played a pivotal role in the medication of different types of cancers; however, they are associated with several side effects and relevance of drug resistance which evoke an immediate need for designing of new anticancer agents with multitargeted effect. Imidazole is a heterocyclic compound privileged with considerable anticancer activities and some imidazole derivatives have already got approval to treat cancer. Many hybrid molecules are available that play an important role in the treatment of cancer like chalcone, pyrazole, purine, triazine etc., and their pharmacophore provide the anticancer drug with low drug resistance and high efficacy, with low chances of toxicity and side effects. This review provides various approaches for the drug development of new safe and efficient antitumor agents imidazole hybrids with other heterocyclic moieties. An attempt has been made to advancement of the anticancer potential of the derivatives and hybrids of imidazole having intact or condensed imidazole moiety in the last decade along with the structure‐activity relationship studies, and mechanism of action.

Nitrogen‐Containing Heterocyclic Scaffolds as EGFR Inhibitors: Design Approaches, Molecular Docking, and Structure‐Activity Relationships

“…[43] Natural products, colours, medicines, organic materials, and notably pharmacologically promising compounds all include N-heterocycles. [4,44] These N-heterocyclic compounds such as triazine, [45] indole, [46] oxadiazole, [47] acridine, [48] benzimidazoles, [49] benzothiazoles, [50] imidazole, [51] isoxazole, [52] thiazolidine, [53] triazoles, [54] quinolines, [55] pyrimidine, [56] pyrazole [57] and quinazolines garnered a lot of interest in recent years due to their wide range of activities. [58] These N-heterocyclic described anticancer effects in numerous types of cancer through limiting cell growth, inducing cell differentiation and apoptosis.…”

Benzimidazole hybrids as anticancer drugs: An updated review on anticancer properties, structure–activity relationship, and mechanisms of action (2019–2021)

“…Azoles could inhibit aurora kinase, cyclin-dependent kinase, cyclo-oxygenase, heat shock protein 90 (HSP90), vascular endothelial growth factor (VEGF), mitotic spindle microtubules, histone deacetylases, TKs, and topoisomerases, and several azole-based chemotherapeutics such as dasatinib, nilotinib, tipifarnib, and tozasertib are being used in clinics to cure various cancers. [29][30][31][32] Thus, hybridization of benzimidazole with azole may open a door for the opportunities for the development of novel anticancer agents.…”

Synthesis and biological research of new imidazolone-sulphonamide-pyrimidine hybrids as potential EGFR-TK inhibitors and apoptosis-inducing agents

“…27 The imidazolone pharmacophore can acquire synergistic activity with other agents and also, re-sensitize that have acquired resistance. 28 Alternatively, sulphonamide and its derivatives are bestowed with diverse biological properties and have received significant attention in the drug development process. 29,30 Moreover, from a chemical structure point of view, the common skeleton of several kinase inhibitors is the pyrimidine ring 31 (Fig.…”