Synthesis, in vitro cytotoxicity, ADME, and molecular docking studies of benzimidazole‐bearing furanone derivatives

Abstract

A series of benzimidazole‐derived–furanones (4a–l) were synthesized, characterized, and explored for their in vitro anticancer activities. The pharmacokinetic parameters assessed revealed that all the compounds followed the Lipinski's rule of five, making them potential drug candidates. Further, the results of anticancer activity revealed that (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐(3,4,5‐trimethoxybenzylidene)furan‐2(3H)‐one (4a), was active against A549, MCF7, and DU145 with an IC50 values of 10.4 ± 0.39, 11.1 ± 0.43, and 10.7 ± 0.19 μM, respectively. While another compound (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐([5‐phenyl]furan‐2‐yl)furan‐2(3H)‐one (4k) also exhibited good activity against A549, MCF7, and DU145 with IC50 values of 11.4 ± 0.39, 9.1 ± 0.43, and 12.7 ± 0.19 μM, respectively. Doxorubicin was used as the standard drug. Further, molecular docking studies were carried out to provide binding mode into the binding sites of vascular endothelial growth factor receptor (VEGFR). Docking scores and binding energies corroborated well with the results of experimental anticancer activity. Pharmacokinetic (ADME) parameters of the potent derivatives were also found to be in an acceptable range. The benzimidazole‐furanonone conjugates seem to be a potential source for the further development of potent cytotoxic agents.

Exploring the Versatility of Benzimidazole Scaffolds as Medicinal Agents: A Brief Update

“…Husain et al prepared various derivatives of furanone appended benzimidazoles, which effectively contribute to cancer therapy [53]. Compound (40) was found active against DU145 and MCF7 whereas compound (41) has got excellent activity against MCF7, A549, and DU145 cell lines (Figure 11).…”

“…Benzene-1,2-diamine undergoes condensation reactions with anthranilic acid, 3, 5-dinitrophenylbenzoic acid, and phenylacetic acid, catalyzed by NH 4 Cl yielded the precursor molecules, which on reaction with electrophile-releasing agents produced the corresponding o-substituted and 1,2-disubstituted benzimidazoles (52) and (53), respectively (Figure 13). In vitro studies of these compounds showed a better activity with a low minimum inhibitory concentration (MIC) value.…”

Design, Synthesis, Molecular Docking, ADME and Biological Evaluation Studies of Some New 1,3,4-oxadiazole Linked Benzimidazoles as Anticancer Agents and Aromatase Inhibitors

“…1 H-NMR (300 MHz, DMSO-d 6 ): δ = 1.35 (3H, t, J=6.90 Hz, -CH3), 3.07-3.20 (4H, m, piperazin), 3.63-3.70 (4H, m, piperazin), 4.10 (2H, q, J=6.93 Hz, -CH2), 4.61 (2H, s, -CH 2 ), 6.97-7.01 (4H, m, Aromatic C-H), 7.02-7.10 (2H, m, Aromatic C-H), 7.52-7.56 (1H, m, benzimidazole-C4), 7.58 (1H, dd, J 1 =8.37 Hz, J 2 =1.56 Hz, benzimidazole-C5), 8.02 (1H, s, benzimidazole-C7), 8.17(2H, d, J= 8.82 Hz, 1,4-disubstituted benzene). 13…”

“…It is observed that hydrogen bond donor and acceptor sites, that is, N1 and N3 in the benzimidazole core, play a critical role in binding to the biological targets [12]. In recent studies, potential anticancer activity has been noted in compounds to which benzimidazole is linked by other heterocyclic rings [13][14][15][16]. The benzimidazole ring has been applied to various marketed anticancer drugs such as bendamustine, veliparip, carbendazim, and nocodazole (Figure 1b).…”

Synthesis, Molecular Docking, and DFT Calculation of a Half‐Strapped BODIPY as Potential EGFR Inhibitor**

“…Molecular docking can help to predict the most energetically favorable binding pose of a ligand to its receptor in terms of the binding energy. [31][32][33] EGFR (epidermal growth factor receptor) is a transmembrane glycoprotein having a mass of ∼ 180 kDa containing-i) an extracellular domain, ii) single transmembrane domain, and iii) intracellular tyrosine kinase domain. [34][35][36] Within the extracellular domain lies a ligandbinding cleft that can interact with a number of various ligands, including EGF and TGF-α.…”