Design, Synthesis, and Anticancer Activity of New Oxadiazolyl‐Linked and Thiazolyl‐Linked Benzimidazole Arylidines, Thioglycoside, and Acyclic Analogs

• Published in: Journal of heterocyclic chemistry Vol. 56; no. 3; pp. 1086 - 1100
• Main Authors: Nassar, Ibrahim F., El kady, Dina S., Awad, Hanem M., El‐Sayed, Wael A.
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.03.2019; Wiley Subscription Services, Inc
• Subjects: Aldehydes; Anhydrides; Anticancer properties; Breast cancer; Cancer; Chemistry; Chemistry, Organic; Derivatives; Docking; Doxorubicin; Hydrazines; Hydrazones; Physical Sciences; Science & Technology; Xylose; POTENT; SERIES; HETEROCYCLES; AGENTS; ANTITUMOR-ACTIVITY; DERIVATIVES; ACYCLONUCLEOSIDES
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.3496

2‐[(4‐Thiazolylmethyl)thio]‐1H‐benzimidazole 3 was prepared and was allowed to react with ethyl chloroactate then with hydrazine hydrate to afford the hydrazide derivative 5, which was then reacted with aromatic aldehydes to afford the corresponding arylidine derivatives 6–9. Heterocyclization of the latter hydrazones with acetic anhydride afforded the substituted 1,3,4‐oxadiazoline derivatives 10–13. In addition, new ((thiazolyl)imidazolyl) oxadiazole thioglycoside and acyclic‐C nucleoside analog were prepared via heterocylization of the hydrazide 5 then glycosylation with α‐acetobromoglucose or condensation with D‐xylose, respectively. All the new compounds were structurally characterized. The anticancer activity of some of the newly synthesized compounds was studied against human breast cancer cells (MCF‐7). The results of the anticancer activity showed that compounds 8, 11, 12, 17, and 18 revealed high activities superior to Doxorubicin; however, the other derivatives showed moderate to low inhibition activities against human breast cancer cells. Docking studies into CDK2 enzyme were investigated, which supported the anticancer activity results.