Current scenario of pyrazole hybrids with in vivo therapeutic potential against cancers

Abstract

Chemotherapeutics occupy a pivotal role in the medication of different types of cancers, but the prevalence and mortality rates of cancer remain high. The drug resistance and low specificity of current available chemotherapeutics are the main barriers for the effective cancer chemotherapy, evoking an immediate need for the development of novel anticancer agents. Pyrazole is a highly versatile five-membered heterocycle with two adjacent nitrogen atoms and possesses remarkable therapeutic effects and robust pharmacological potency. The pyrazole derivatives especially pyrazole hybrids have demonstrated potent in vitro and in vivo efficacies against cancers through multiple mechanisms, inclusive of apoptosis induction, autophagy regulation, and cell cycle disruption. Moreover, several pyrazole hybrids such as crizotanib (pyrazole-pyridine hybrid), erdafitinib (pyrazole-quinoxaline hybrid) and ruxolitinib (pyrazole-pyrrolo [2,3-d]pyrimidine hybrid) have already been approved for the cancer therapy, revealing that pyrazole hybrids are useful scaffolds to develop novel anticancer agents. The purpose of this review is to summarize the current scenario of pyrazole hybrids with potential in vivo anticancer efficacy along with mechanisms of action, toxicity, and pharmacokinetics, covering papers published in recent 5 years (2018-present), to facilitate further rational exploitation of more effective candidates.