Novel Benzimidazole/Hydrazone Derivatives as Promising Anticancer Lead Compounds: Design, Synthesis, and Molecular Docking Study

Abstract

A novel series of benzimidazole-hydrazone derivatives was designed and synthesized as a potential anti-cancer agents. The structure of the target compounds was assured using different spectroscopic methods such as IR, 1 H NMR, 13 C NMR and elemental analysis. These new compounds were examined and evaluated for their antiproliferative activities against 60 different cell lines. Combination of benzimidazole scaffold with hydrazone group exhibited promising anti-cancer activity. Compounds 3a and 3b showed significant activity against different cancer cells lines between 50-84 % of growth inhibition. A molecular modeling study for compounds 3a and 3b into VEGFR-2 active site was performed with reasonable docking scores.

Synthesis, DFT Molecular Geometry and Anticancer Activity of Symmetrical 2,2′-(2-Oxo-1H-benzo[d]imidazole-1,3(2H)-diyl) Diacetate and Its Arylideneacetohydrazide Derivatives

“…The IC50 values ( Table 4 ) for HCT-116 were 29.5 + 4.53 µM, 57.9 + 7.01 µM, 40.6 + 5.42 µM for 6a , 6b and 6c , respectively. These results indicate a high capacity of these compounds to inhibit HCT-116 growth when compared, for example, to novel benzimidazole derivatives synthesized by Morcoss et al, which inhibited the proliferation of HCT-116 by approximately 56% at a concentration of 10 mM [ 1 ]. Furthermore, some novel pyrazole-benzimidazole derivatives synthesized by Ren et al have demonstrated significant antiproliferative activity against HCT-116 cells with the IC50 values of 4.33, 5.15 and 4.84 μM [ 65 ].…”

“…Cancer is one of the world’s biggest medical challenges [ 1 ]. Cancer is characterized by cell cycle disruption, which inhibits cell differentiation and promotes uncontrollable cell growth [ 2 ].…”

Design, Synthesis, Docking Study, and Antiproliferative Evaluation of Novel Schiff Base–Benzimidazole Hybrids with VEGFR-2 Inhibitory Activity

“…Target compounds 3a – o were chemically synthesized as shown in Scheme 1 . Compounds 1a , b were prepared according to the reported methods [ 27 ]. The chemical structures of such compounds were proven by matching their spectral data with the reported data [ 27 ].…”

“…Compounds 1a , b were prepared according to the reported methods [ 27 ]. The chemical structures of such compounds were proven by matching their spectral data with the reported data [ 27 ]. The key intermediates compounds, benzimidazole-hydrazone 2a , b , were prepared by heating compounds 1a , b with hydrazine hydrate at reflux temperature for 12 h. The final target benzimidazole–Shiff hybrids 3a – o were prepared by reaction of the benzimidazole hydrazone derivatives 2a , b with the appropriate acetophenone or aldehyde derivatives in ethanol in the presence of few drops of acetic acid as catalyst under reflux conditions.…”

Synthesis and characterization of novel conformers of (E)‐2‐(3‐nitro‐H‐imidazo[1,2‐a]pyridin‐2‐ylthio)‐N′‐benzylideneacetohydrazide derivatives

“…N-acylhydrazones are featured by (CO-NH-N=CH) moiety, which when connected to heterocyclic scaffold, very often leads to compounds with interesting biological activities, including anticancer, [1,2] antibacterial, [3][4][5] antiviral, [6,7] and antihypertensive [8] properties. The molecules based on imidazo [1,2-a]pyridine are heterobicyclic compounds that also exhibited antimicrobial [9][10][11] antiinflammatory, [12] anticancer, [13,14] and antiparasitic [15] properties, among many others.…”