Scaffold hybridization in generation of indenoindolones as anticancer agents that induce apoptosis with cell cycle arrest at G2/M phase

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 7; pp. 2474 - 2479
• Main Authors: Kashyap, Maneesh, Das, Dipon, Preet, Ranjan, Mohapatra, Purusottam, Satapathy, Shakti Ranjan, Siddharth, Sumit, Kundu, Chanakya N., Guchhait, Sankar K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.04.2012; Elsevier
• Subjects: 5-Fluorouracil; Animals; Anticancer; anticarcinogenic activity; antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Antitumor activity; Antitumor agents; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Biomarkers - metabolism; Cancer; Cell cycle; Cell Survival - drug effects; Cercopithecus aethiops; Etoposide; Etoposide - pharmacology; Flow Cytometry; Fluorouracil - pharmacology; G2 Phase Cell Cycle Checkpoints - drug effects; HEK293 Cells; Humans; Hybrid; Indenes - chemical synthesis; Indenes - pharmacology; Indenoindolones; Indoles - chemical synthesis; Indoles - pharmacology; Inhibitory Concentration 50; kidney neoplasms; Medical sciences; Pharmacology. Drug treatments; scaffolds; Toxicity; Vero Cells; Hybrid; Indenoindolones; Anticancer; Cell cycle; Apoptosis; Antineoplastic agent; Drug; Cell death; G2 Phase; Hybridization; Antimitotic; Research and development
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.02.007

Scaffold hybridization of several natural and synthetic anticancer leads led to the consideration of indenoindolones as potential novel anticancer agents. A series of these compounds were prepared by a diversity-feasible synthetic method. They were found to possess anticancer activities with higher potency compared to etoposide and 5-fluorouracil in kidney cancer cells (HEK 293) and low toxicity to corresponding normal cells (Vero). They exerted apoptotic effect with blocking of cell cycle at G2/M phase.