Synthesis of indolo/pyrroloazepinone-oxindoles as potential cytotoxic, DNA-intercalating and Topo I inhibitors.
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| Abstract |
A series of 17 indolo/pyrroloazepinone-oxindole conjugates was synthesized and evaluated for their antiproliferative activity against a panel of selected human cancer cell lines including A549 (lung cancer), HCT116 (colon cancer), MCF7 (breast cancer), and SK-MEL-28 (melanoma). Among the synthesized molecules (14a-m and 15a-d), compound 14d displayed remarkable activity against A549, HCT116 and SK-MEL-28 cells with IC50 values < 4 μM with the best cytotoxicity and a 13-fold selectivity towards lung cancer cells (IC50 value of 2.33 μM) over the normal rat kidney cells (NRK). Further, 14d-mediated apoptosis affected the cellular and nuclear morphology of the cancer cells in a dose-dependent manner. Wound healing and clonogenic assays inferred the inhibition of cell growth and migration. Target-based studies of compound 14d corroborated its DNA-intercalative capability and Topo I inhibitory activity which have been fortified by molecular modeling studies. Finally, the drug-likeness of the potent compound was determined by performing in silico ADME/T prediction studies.
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| Authors | Manasa Kadagathur, Arbaz Sujat Shaikh, Biswajit Panda, Joel George, Regur Phanindranath, Dilep Kumar Sigalapalli, Nagesh A Bhale, Chandraiah Godugu, Narayana Nagesh, Nagula Shankaraiah, Neelima D Tangellamudi |
| Journal | Bioorganic chemistry (Bioorg Chem) Vol. 122 Pg. 105706 (05 2022) ISSN: 1090-2120 [Electronic] United States |
| PMID | 35240414 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 Elsevier Inc. All rights reserved. |
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