Amidoximes and their Cyclized Analogue Oxadiazoles as New Frontiers in Chemical Biology: Mini Review

Abstract: This comprehensive review delves into the medicinal chemistry of amidoxime and 1,2,4- oxadiazole scaffolds. These scaffolds have been modified to address bacterial infections, malaria, inflammation, Alzheimer's disease, and cancer, yielding novel lead compounds with significant therapeutic potential. The review scrutinizes recently developed bioactive candidates, highlighting their antibacterial and anti-biofilm properties through the targeting of essential bacterial replication and virulence factors. In oncology, these derivatives exhibit promise by interacting with critical macromolecules, presenting diverse mechanisms of action. Notably, amidoxime hybrids have shown potential in inhibiting indoleamine 2,3-dioxygenase 1 (IDO1), whereas oxadiazole hybrids demonstrate anti-proliferative effects by targeting the epidermal growth factor receptor (EGFR). These hybrids also display dual inhibition of cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX), indicating significant anti-inflammatory potential. In the context of Alzheimer's disease, oxadiazoles are emerging as promising agents targeting human carbonic anhydrase (hCA) I and II enzymes. Additionally, they exhibit anti-malarial activity by targeting the Plasmodium parasite. The review further examines marketed drugs such as Ximelagatran, Upamostat, and Naldemedine, underscoring their versatile and targeted therapeutic approaches. The aim of this review is to guide medicinal chemists in synthesizing amidoximes and oxadiazoles with enhanced efficacy and reduced side effects. These scaffolds hold promising potential for future development and clinical trials.