title: Indenoindolone derivatives as topoisomerase II-inhibiting anticancer agents.
abstract: Based on known heterocyclic topoisomerase II inhibitors and anticancer agents, various indenoindolone derivatives were predicted as potential topoisomerase II-inhibiting anticancer agents. They are hydrazones, (thio)semicarbazones, and oximes of indenoindolones, and indenoindolols. These derivatives with suitable substitutions exhibited potent specific inhibition of human DNA TopoIIα while not showing inhibition of topoisomerase I and DNA intercalation, despite the fact that parent indenoindolones are known poor/moderate inhibitors of topoisomerase II. The potent topoisomerase II inhibitor indenoindolone derivatives exhibited good anticancer activities compared to etoposide and 5-fluorouracil, and relatively low toxicity to normal cells. These derivatizations of indenoindolones were found to result in enhancement of anticancer activities.
authors: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Mohali, Punjab 160062, India.
authors: Maneesh
authors: M
authors: Kashyap
authors: Somnath
authors: S
authors: Kandekar
authors: Ashish T
authors: AT
authors: Baviskar
authors: Dipon
authors: D
authors: Das
authors: Ranjan
authors: R
authors: Preet
authors: Purusottam
authors: P
authors: Mohapatra
authors: Shakti Ranjan
authors: SR
authors: Satapathy
authors: Sumit
authors: S
authors: Siddharth
authors: Sankar K
authors: SK
authors: Guchhait
authors: Chanakya N
authors: CN
authors: Kundu
authors: Uttam C
authors: UC
authors: Banerjee
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004250:DNA Topoisomerases, Type II / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D059005:Topoisomerase II Inhibitors; C057286:indenoindole; D004250:DNA Topoisomerases, Type II