title: 4β-[4'-(1-(Aryl)ureido)benzamide]podophyllotoxins as DNA topoisomerase I and IIα inhibitors and apoptosis inducing agents.
abstract: A series of 4β-[4'-(1-(aryl)ureido)benzamide]podophyllotoxin congeners (11a-l) were synthesized and evaluated for their cytotoxic activity against six human cancer cell lines. Some of the compounds like 11a, 11h, 11k and 11l showed significant anti-proliferative activity in Colo-205 cells and were superior to etoposide. The flow-cytometric analysis studies indicated that these compounds show strong G1 cell cycle arrest, as well exhibited improved inhibitory activities on DNA topoisomerase I and IIα enzymes. These compounds induce apoptosis by up regulating caspase-3 protein as observed by ELISA and Western blotting analysis. In addition, a brief structure-activity relationship studies within the series along with docking results of representative compounds 11a, 11h, 11k, 11l were presented.
authors.affiliation: Medicinal Chemistry and Pharmacology, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India. ahmedkamal@iict.res.in
authors.forename: Ahmed
authors.initials: A
authors.lastname: Kamal
authors.forename: Paidakula
authors.initials: P
authors.lastname: Suresh
authors.forename: M Janaki
authors.initials: MJ
authors.lastname: Ramaiah
authors.forename: T
authors.initials: T
authors.lastname: Srinivasa Reddy
authors.forename: Ravi Kumar
authors.initials: RK
authors.lastname: Kapavarapu
authors.forename: Bolla Narasimha
authors.initials: BN
authors.lastname: Rao
authors.forename: Syed
authors.initials: S
authors.lastname: Imthiajali
authors.forename: T
authors.initials: T
authors.lastname: Lakshminarayan Reddy
authors.forename: S N C V L
authors.initials: SN
authors.lastname: Pushpavalli
authors.forename: Nagula
authors.initials: N
authors.lastname: Shankaraiah
authors.forename: Manika
authors.initials: M
authors.lastname: Pal-Bhadra
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000737:chemistry*; D001665:Binding Sites; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000737:chemistry* / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D011034:Podophyllotoxin / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C037689:benzamide; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D011034:Podophyllotoxin
keywords: Cell cycle; Cytotoxicity; Etoposide; Podophyllotoxin; Topoisomerase-I enzyme; Topoisomerase-IIα enzyme