Synthesis of 2-aryl-1,2,4-oxadiazolo-benzimidazoles: Tubulin polymerization inhibitors and apoptosis inducing agents

1,2,4- and 1,3,4-Oxadiazoles as Scaffolds in the Development of Antiparasitic Agents

“…This might be explained by the less aromatic profile of this heterocycle, as seen in Figure 12. 41 Kamal et al 42 reported a series of 1,2,4-oxadiazolic derivatives, such as 19a-b, which tend to form hydrophobic interactions between the heterocycle and α-Thr179 apart from π-π stacking with β-Asn258 on the colchicine binding site of bovine tubulin ( Figure 13). The formation of the 1,2,4-oxadiazolic ring via amidoxime route needs an acylating agent, which carries the substituent group that will be positioned at C 5 .…”

“…To do so, they first reacted differently substituted cyanamides (40) in the presence of hydroxylamine hydrochloride and diisopropylethylamine (DIPEA). Then, the N-hydroxide guanidine intermediates (41) were reacted with properly substituted benzoic acids (42) in the presence of HATU and DIPEA. The two-step reaction was carried in CH 2 Cl 2 at room temperature overnight, followed by reflux in 1,2-dichloroethane (DCE) for 5 h, yielding the desired 1,2,4-oxadiazole derivatives (43) (Scheme 7).…”

Synthesis, Crystal Study, and Anti-Proliferative Activity of Some 2-Benzimidazolylthioacetophenones towards Triple-Negative Breast Cancer MDA-MB-468 Cells as Apoptosis-Inducing Agents

“…Structures of some reported benzimidazoles I – VIII , by other research groups, with anti-proliferative activity against triple-negative breast cancer MDA-MB-468 cells [22,23,24,25,26,27]. …”

“…Attaching a heterocyclic moiety, 5- tert -butyl-1 H -pyrazol-3-yl, in position 1 and an aryl moiety, 4-chlorophenyl, in position 2 of benzimidazole core resulted in compound I (NSC: 751047) with good anti-proliferative activity against MDA-MB-468 (IC 50 = 2.4 µM) [22] (Figure 1), while substitution of position 2 of 5-flouro and 5-methoxybenzimidazole with 1,2,4-oxadiazole moiety through a phenyl ring afforded compounds II and III , respectively, (NSC: 761109 and 761814) with IC 50 values of 3.01 and 6.54 µM, respectively, against MDA-MB-468 [23] (Figure 1). Moreover, introduction of different aryl groups through a pyrazole linker at position 2 of the benzimidazole core, as in compounds IV and V (NSC: 768400 and 768399), achieved significant efficacy against MDA-MB-468 (IC 50 values of 0.93 and 3.5 µM, respectively) [24] (Figure 1).…”

Design and synthesis of 4′-O-alkylamino-tethered-benzylideneindolin-2-ones as potent cytotoxic and apoptosis inducing agents

“…Therefore, apoptosis inducing effect of compounds 5j, 5o and 5r were examined on MDA-MB-231 cells using the Hoechst nuclear staining (Hoechst 33242) assay. 38 Hoechst 33242 is the cell permeable nuclear staining dye, which emits blue fluorescence and stains the nucleus of the live cells as light blue, whereas the apoptotic cell nuclei appear as bright blue owing to chromatin condensation. MDA-MB-231 cells were stained with Hoechst 33242 following the treatment with the IC 50 concentrations of compounds 5j, 5o and 5r, and cells were observed for nuclear morphological changes under fluorescence microscope.…”