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

Article abstract of DOI:10.1016/j.ejmech.2020.112870

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.

Full text of DOI:10.1016/j.ejmech.2020.112870

Journal Pre-proof
Design, Synthesis and Screening of Benzimidazole Containing Compounds with
Methoxylated Aryl Radicals as Cytotoxic Molecules on (HCT-116) Colon Cancer Cells
Ryad, M. Noha, M.K. El hamid, M. Mohsen Ismail, R. Mohammed Manal, Elmeligie
Salwa
PII:
S0223-5234(20)30842-4
DOI:
https://doi.org/10.1016/j.ejmech.2020.112870
EJMECH 112870
Reference:
To appear in: European Journal of Medicinal Chemistry
Received Date: 19 June 2020
Revised Date: 21 September 2020
Accepted Date: 21 September 2020
Please cite this article as: R.,.M. Noha, M.K. El hamid, M.M. Ismail, R.M. Manal, E. Salwa, Design,
Synthesis and Screening of Benzimidazole Containing Compounds with Methoxylated Aryl Radicals
as Cytotoxic Molecules on (HCT-116) Colon Cancer Cells, European Journal of Medicinal Chemistry,
https://doi.org/10.1016/j.ejmech.2020.112870.
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Highlights
- the molecules were designed as dual antitumor and radiosensitizer agents .
- Compounds 11b exhibited potent cytotoxic activity on HCT-116 cancer cells higher
than camptothecin (CPT).
-in vitro topoisomerase assay correlated cytotoxicity of molecule 11b to DNA synthesis
inhibition.
-Compound (11b) could regulate the radio-sensitizing activity of the (HCT-116) cells by
modulating the Chromosomal Instability of Multipolar Mitosis (MM), Mitotic
Catastrophe (MC), Binucleated Cells (BN), Micronuclei (MN), Nuclear Bleb (NB), and
Apoptotic Cells (AC).

Conflict of interest:
The authors have declared no conflict of interest.