No abstract

WEE1 is a checkpoint kinase critical for mitotic events, especially in cell maturation and DNA repair. Most cancer cells' progression and survival are linked with elevated levels of WEE1 kinase. Thus, WEE1 kinase has become a new promising druggable target. A few classes of WEE1 inhibitors are designed by rationale or structure-based techniques and optimization approaches to identify selective acting anticancer agents. The discovery of the WEE1 inhibitor AZD1775 further emphasized WEE1 as a promising anticancer target. Therefore, the current review provides a comprehensive data on medicinal chemistry, synthetic approaches, optimization methods, and the interaction profile of WEE1 kinase inhibitors. In addition, WEE1 PROTAC degraders and their synthetic procedures, including a list of noncoding RNAs necessary for regulation of WEE1, are also highlighted. From the standpoint of medicinal chemistry, the contents of this compilation serve as an exemplar for the further design, synthesis, and optimization of promising WEE1-targeted anticancer agents.

Lupeol is one of the most important metabolite in the class of terpenoids and possess excellent anticancer, anti-inflammatory, anti-diabetic activities etc. In the present study, the different thiazoles and oxazoles bearing lupeol derivatives were prepared to enhance their biological activity. Initially, the in vitro cytotoxic activity results showed that the synthesized lupeol derivatives (9a-9j and 10a-10e) showed significant activity against various cancer cells and the compounds 9h and 10b exhibited excellent activity against CAL27 cells. Further, these compounds 9h and 10b arrest the cell cycle at S phase and induce the late apoptosis in CAL27 cells by downregulating the BcL2 and vimentin expression and upregulating the Bax gene expression. Moreover, the lupeol derivatives showed dose-dependent anti-inflammatory activity by inhibiting the secretion of IL-6 cytokines in LPS-induced Raw 264.7 cells. Together, these results clearly indicated that the thiazoles and oxazoles bearing lupeol derivatives can used as chemotherapeutic drugs against cancer and inflammatory diseases.