A series of novel N-substituted-2-amino-3,4,5-trimethoxybenzoylindoles was synthesized
and assessed against human cancer cell lines of breast (MCF-7) and colon (HT-29). The two derivatives
7a and 11a, in which the hydrogen atom at position 1 was substituted by a methyl and a benzoyl
group respectively, showed significant cytotoxic activity GI50 against MCF-7 (0.045 µM), HT-29
(4.25 µM) and MCF-7 (0.035 µM) HT-29 (0.856 µM). Molecular docking studies indicated that compounds
7a and 11a possess hydrogen bond interaction between SH group of Cys 241 of receptor molecule
and para position of trimethoxyphenyl group of benzoyl moiety, while compound 11a has an extra
hydrogen bond interaction between Ser 178 of receptor molecule and keto group of benzoyl moiety.
The compound 11a showed high solvent-exposed penalty due to the presence of phenyl ring of benzoyl
molecule, thus compound 11a showed low Gscore and lesser potent as compared to 7a.
Keywords: Anticancer, combretastatin A-4, docking, N-substituted-2-amino-3, 4, 5-trimethoxybenzoylindole, synthesis, MCF-7.
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