2. Academic Validation
  3. Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells

Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells

  • Eur J Med Chem. 2021 Jan 1:209:112870. doi: 10.1016/j.ejmech.2020.112870.
Ryad M Noha 1,  Mohammed K Abdelhameid 2,  M Mohsen Ismail 3,  Manal R Mohammed 4,  Elmeligie Salwa 5
Affiliations

Affiliations

  • 1 Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing, Misr University for Science & Technology, Giza, P.O. Box 77, Egypt.
  • 2 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11561, Egypt. Electronic address: mohamed.sayed@pharma.cu.edu.eg.
  • 3 Pharmaceutical Organic Chemistry Department, College of Pharmaceutical Science and Drug Manufacturing, Misr University for Science & Technology, Giza, P.O. Box 77, Egypt; Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11561, Egypt.
  • 4 Department of Radiation Biology, National Center for Radiation Research and Technology, Cairo, 11787, Egypt.
  • 5 Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, 11561, Egypt.
PMID: 33158579 DOI: 10.1016/j.ejmech.2020.112870
Abstract

A novel series of benzimidazole derivatives with methoxylated aryl groups was designed and synthesized as molecules with potential cytotoxic activity. In vitro cytotoxic activity over HCT-116 cells showed that N-(benzimidazothiazolone)acetamides 11a, 11b and 11c were found to be the most cytotoxic compounds compared camptothecin (CPT). The tested compounds had a dual Topoisomerase I-β (Topo I-β) and tubulin inhibiting activities when compared to CPT and Podophyllotoxin (Podo) where, compounds l0a, l0b, 11a and 11b exhibited a potent inhibitory activity on Topo I-β Enzyme in nano-molar concentration, on the Other hand, compounds 12b and 13b exhibited the best inhibitory activity β-tubulin polymerization. Results of the cell cycle analysis as well as the results of annexin-V on HCT-116 cells showed that benzimidazothiazoles 12b and 13b had a pro-apoptotic activity higher than CPT by 1.33- and 1.30-folds, respectively. Moreover, the concentration of p53, Bax/Bcl-2 ratio and Caspase 3/7 increased in compounds l0b, 11b, l2b, 13b, especially, compounds 11b and 13b exhibited an increased level of these mediators than CPT. Finally, compound 11b regulated the radiosensitizing activity of the HCT-116 cells by modulating the chromosomal instability.

Keywords

Camptothecin; HCT-116; Podophyllotoxin; Radiation; Topoisomerase; Tubulin.

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