Synthesis of N-substituted-2-amino-3,4,5-trimethoxybenzoylindoles as Novel Anticancer Agents

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.