Groundbreaking Anticancer Activity of Highly Diversified Oxadiazole Scaffolds

Abstract

Nowadays, an increasing number of heterocyclic-based drugs found application in medicinal chemistry and, in particular, as anticancer agents. In this context, oxadiazoles—five-membered aromatic rings—emerged for their interesting biological properties. Modification of oxadiazole scaffolds represents a valid strategy to increase their anticancer activity, especially on 1,2,4 and 1,3,4 regioisomers. In the last years, an increasing number of oxadiazole derivatives, with remarkable cytotoxicity for several tumor lines, were identified. Structural modifications, that ensure higher cytotoxicity towards malignant cells, represent a solid starting point in the development of novel oxadiazole-based drugs. To increase the specificity of this strategy, outstanding oxadiazole scaffolds have been designed to selectively interact with biological targets, including enzymes, globular proteins, and nucleic acids, showing more promising antitumor effects. In the present work, we aim to provide a comprehensive overview of the anticancer activity of these heterocycles, describing their effect on different targets and highlighting how their structural versatility has been exploited to modulate their biological properties.

Green Synthetic Approach: An Efficient Eco-Friendly Tool for Synthesis of Biologically Active Oxadiazole Derivatives

“…[71][72][73][74]. Hence, oxadiazole is considered a significant heterocyclic core and becomes a major scaffold for the development of new drug candidates because of its potential to be involved in the binding interactions with different targets or receptors with suitable metabolic profile [75][76][77][78].…”

1,3,4-Oxadiazole N-Mannich Bases: Synthesis, Antimicrobial, and Anti-Proliferative Activities

“…In addition, there is a growing interest in the chemotherapeutic activities of 2,5-disubstituted-1,3,4-oxadiazoles as antibacterial [ 10 , 11 , 12 ], antifungal [ 13 , 14 , 15 ], antitubercular [ 16 , 17 ], and antiviral [ 18 , 19 , 20 , 21 ] agents. Moreover, 1,3,4-Oxadiazole-2(3 H )-thiones, their thioether derivatives and 3-aminomethyl analogues ( N -Mannich bases) are the most interesting for their anticancer activities [ 21 , 22 ].…”

“…In addition, there is a growing interest in the chemotherapeutic activities of 2,5-disubstituted-1,3,4-oxadiazoles as antibacterial [ 10 , 11 , 12 ], antifungal [ 13 , 14 , 15 ], antitubercular [ 16 , 17 ], and antiviral [ 18 , 19 , 20 , 21 ] agents. Moreover, 1,3,4-Oxadiazole-2(3 H )-thiones, their thioether derivatives and 3-aminomethyl analogues ( N -Mannich bases) are the most interesting for their anticancer activities [ 21 , 22 ]. The 1,3,4-Oxadiazole derivatives exert their anticancer activities via different mechanisms, such as targeting epidermal growth factor receptors (EGFR) [ 23 ], vascular endothelial growth factor receptors (VEGF) [ 24 ], focal-adhesion kinase (FAK) [ 25 , 26 ], histone deacetylases (HDAC) [ 27 , 28 ], methionine aminopeptidase (MetAP) [ 29 ], NF-κB (nuclear factor κB) [ 30 ], poly(ADP-ribose) polymerase (PARP-1) [ 31 ], thymidine phosphorylase (TP) [ 32 ], telomerase [ 33 ], thymidylate synthase (TS) [ 34 ], zinc-finger protein 143 (ZNF143) [ 35 ], and tubulin polymerase [ 36 ].…”

Synthesis, insecticidal activities, and structure–activity relationships of 1,3,4‐oxadiazole‐ring‐containing pyridylpyrazole‐4‐carboxamides as novel insecticides of the anthranilic diamide family

“…These derivatives show significantly higher insecticidal activity than other heterocyclic derivatives. Structural modification with heterocyclic oxadiazole rings, especially five-membered regioisomeric 1,2,4-and 1,3,4-oxadiazoles, imparts potent biological properties and increases anticancer activity [22].…”