Synthesis, Characterization and Antitumor Activity of Benzimidazole Phosphonate Derivatives

Document Type : Original Article

Authors

1 Chemical Industries Research Institute, National Research Centre, Elbehouth St, Dokki, Cairo 12622, Egypt

2 Department of Chemistry of Natural and Microbial Products, Institute of Pharmaceutical and Drug Industries, National Research Centre, Dokki, Cairo, Egypt

3 Department of Tanning Materials and Leather Technology, National Research Centre, 33 El-Bohouth St. (former El Tahrir St.), P.O. 12622, Dokki, Giza, Egypt.

Abstract

A series of Benzimidazole derivatives were obtained via reaction of 2-chloro-1H-benzo[d]imidazole (1) with morpholine, which produce benzo[d]imidazol-yl-morpholine 2 that react with chloroacetonitrile to give (benzo[d]imidazol-yl)acetonitrile 3, by its next reaction with hydrazine hydrate afforded the key intermediate 4, that afford thiadiazole derivatives 5 by its reaction with carbon disulfide via cyclization reaction. Alkylation of compound 5 with ethyl bromoacetate, afforded benzo[d]imidazolo derivative 6, that react with thioglycolic acid to give thiazolidine compound in suitable conditions. Also Benzimidazole 1 reacted with various Wittig Horner reagents in DMF to afford phosphoryl and phosphonates derivatives 12a-e in moderate yields. On the other hand, 1 react with trialkyl phosphites to yield the known phosphonates derivatives 14a-c in high yields, also we obtained the same products by reacting 1 with dialkyl phosphites. In addition, hexaalkyltriamidophosphites were applied to 1 in ethanol to afford phosphonic diamide derivatives 17a-c in high yields through addition-elimination reaction. Antitumor activity of the newly synthesized compounds were tested on three cell lines of breast (MCF7) and liver (HepG2) carcinoma cell lines and HCT-116 cancer cells together with human healthy cell line (BJ-1) using the MTT assay. Most compounds suppressed three cancer cells (HCT-116, HepG2 and MCF-7) and exhibited considerable anticancer properties in a dose-dependent manner

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Egyptian Journal of Chemistry
Volume 67, Issue 13 - Serial Number 13
In Loving Memory of Late Professor Doctor ””Mohamed Refaat Hussein Mahran””
December 2024
Pages 443-452

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History

  • Receive Date: 24 December 2023
  • Revise Date: 24 January 2024
  • Accept Date: 08 February 2024

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