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Design, Synthesis, Biological Evaluation, and in Silico Studies of Novel N-Substituted-2-(3,4,5-Trimethoxyphenyl)-1H-Benzo[D]Imidazole-6-Carboxamides As Promising Anticancer Agents Publisher



Dastyafteh N1 ; Negahdaripour M2, 3 ; Sayahi MH4 ; Emami M2 ; Ghasemi Y2, 3 ; Safaei E5 ; Azizian H6 ; Pakrouh Jahromi Z2, 3 ; Asadi M6 ; Mohajeritehrani MR1 ; Zare F2 ; Shahidi M7 ; Pooraskari Z7 ; Sajjadijazi SM1 Show All Authors
Authors
  1. Dastyafteh N1
  2. Negahdaripour M2, 3
  3. Sayahi MH4
  4. Emami M2
  5. Ghasemi Y2, 3
  6. Safaei E5
  7. Azizian H6
  8. Pakrouh Jahromi Z2, 3
  9. Asadi M6
  10. Mohajeritehrani MR1
  11. Zare F2
  12. Shahidi M7
  13. Pooraskari Z7
  14. Sajjadijazi SM1
  15. Larijani B1
  16. Mahdavi M1
  17. Ranjbar S2

Source: RSC Advances Published:2024


Abstract

Novel benzimidazole-based derivatives were synthesized and their cytotoxic activities were evaluated against two human cancer cells, SW480 and A549, and the normal human MRC-5 cells, using the MTT assay. N-(2,4-Dimethoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-1H-benzo[d]imidazole-6-carboxamide (5o) showed excellent cytotoxicity with IC50 values of 0.15 ± 0.01 and 3.68 ± 0.59 μM against A549 and SW480. Compound 5o had 38.5-, 62.9- and 3.1-fold superior cytotoxicity than cisplatin (IC50 = 5.77 ± 1.60 μM), etoposide (IC50 = 9.44 ± 1.98 μM), and doxorubicin (IC50 = 0.46 ± 0.02 μM), respectively against A549 cells. Moreover, 5o exhibited high selectivity towards A549 (SI = 794.6) and SW480 (SI = 32.4) cancer cells compared with the normal MRC-5. Further studies revealed the ability of 5o to induce apoptosis and arrest the cell cycle at the S phase in A549 cells. Molecular docking studies revealed 5o was well accommodated within the pocket of topoisomerase IIα-DNA, as a possible target. Molecular dynamics simulation studies confirmed the stability of the 5o-IIα-DNA complex. Compound 5o was predicted to have appropriate drug-likeness and pharmacokinetic properties. © 2024 The Royal Society of Chemistry.
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