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.
Highlights
Zhang et al identified an efficient focal adhesion kinase (FAK) inhibitor, 28 (Figure 6), testing a family of compounds whose chemical structures were based on 1,3,4-oxadiazoles conjugated to benzotriazole unit [47]
Topo II inhibitors became clinically useful as chemotherapeutical agents, and in this slice Rao et al have developed imidazopyridinyl-1,3,4-oxadiazole conjugates, among which 38 (Figure 7) was able to affect the catalytic activity of this specific enzyme [58]
The overview of oxadiazoles anticancer activity reported highlights the extensively use of this class of heterocyclic compounds in medicinal chemistry, further confirmed by the presence of several commercially available drugs based on these interesting scaffolds
Summary
Heterocyclic compounds are recognized as intriguing scaffffoollddss too incorporate in bioactive small moleeccuulleess,,dduueetotoththeecrcurcuicailarlorleoltehatht ahtetheertoeartooamtosmcosvceorvinerpihnypsihoylosgioicloagl ipcraolcpesrsoecse.sIsneds.eeIndd, emeodr,emthoarne 8th5a%no8f5b%ioolof gbicoalollgyicaacltliyveactoimvepcooumndpsoubneadrsabtelaerasat olenaesthoetneerohceyteclrioccmycoliectmy o[1ie].ty [1]. TThhee bbeesstt aannttiipprroolliiffeerraattiivvee eeffffeeccttiivveenneessss wwaass oobbttaaiinneedd oonn HHeeppGG22 lliinnee bbyy ccoommppoouunnddss 33 aanndd 44 ((FFiigguurree 33)) wwiitthh IICC5500 vvaalluueess ooff 77..2211 μμMM aanndd 88..5544 μμMM,, rreessppeeccttiivveellyy. Biological activity was evaluated on the same four cancer cell lines, highlighting a broad-spectrum of antiproliferative effects In this case, the best results were obtained on HepG2 and SW1116 cells with compounds 6 and 7 (HepG2, IC50 = 4.22–5.79 μM; SW1116, IC50 = 2.46–5.06 μM; Figure 3), which are more or efficient than positive control Staurosporine (HepG2, IC50 = 6.73 μM; SW1116, IC50 = 4.95 μM). It has been predicted that compound 6 interacts with telomerase binding site through five hydrogen bonds: three involved oxadiazole moiety and Arg194 as well as Gln308 residues, the other two were correlated to pyrazine’s nitrogen atom and Lys189 [30]. While for 8, the interaction with the telomerase binding site is unconnected to the presence of oxadiazole unit, the 1,3,4-oxadiazole in 9 is responsible for two H-bonds that involved Gln308 and Arg194 residues, as predicted by automated docking studies [31]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
