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Synthesis, in vitro cytotoxicity, ADME, and molecular docking studies of benzimidazole‐bearing furanone derivatives
Author(s) -
Husain Asif,
Bhutani Medha,
Parveen Shazia,
Khan Shah Alam,
Ahmad Aftab,
Iqbal Md Azhar
Publication year - 2021
Publication title -
journal of the chinese chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.329
H-Index - 45
eISSN - 2192-6549
pISSN - 0009-4536
DOI - 10.1002/jccs.202000130
Subject(s) - chemistry , adme , benzimidazole , docking (animal) , du145 , stereochemistry , lipinski's rule of five , cytotoxicity , in vitro , pharmacophore , pharmacology , in silico , biochemistry , organic chemistry , cancer cell , medicine , nursing , cancer , lncap , gene
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‐(1 H ‐benzo[ d ]imidazol‐2‐yl)‐3‐(3,4,5‐trimethoxybenzylidene)furan‐2(3 H )‐one ( 4a ), was active against A549, MCF7, and DU145 with an IC 50 values of 10.4 ± 0.39, 11.1 ± 0.43, and 10.7 ± 0.19 μM, respectively. While another compound ( E )‐5‐(1 H ‐benzo[ d ]imidazol‐2‐yl)‐3‐([5‐phenyl]furan‐2‐yl)furan‐2(3 H )‐one ( 4k ) also exhibited good activity against A549, MCF7, and DU145 with IC 50 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.