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Design, synthesis and screening of benzimidazole containing compounds with methoxylated aryl radicals as cytotoxic molecules on (HCT-116) colon cancer cells
- Source :
- European Journal of Medicinal Chemistry. 209:112870
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
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.
- Subjects :
- Radiation-Sensitizing Agents
Benzimidazole
Antineoplastic Agents
Apoptosis
Caspase 3
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Chromosomal Instability
Drug Discovery
medicine
Humans
Cytotoxic T cell
030304 developmental biology
Pharmacology
chemistry.chemical_classification
0303 health sciences
biology
010405 organic chemistry
Aryl
Topoisomerase
Organic Chemistry
General Medicine
HCT116 Cells
Tubulin Modulators
0104 chemical sciences
Podophyllotoxin
Enzyme
chemistry
Biochemistry
Drug Design
Colonic Neoplasms
biology.protein
Benzimidazoles
Drug Screening Assays, Antitumor
Camptothecin
medicine.drug
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 209
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....ee88765412e2422807007afd13a6060b