title: An overview on 2-arylquinolin-4(1H)-ones and related structures as tubulin polymerisation inhibitors.
abstract: Agents that interfere with tubulin function have a broad anti-tumour spectrum and they represent one of the most significant classes of anti-cancer agents. In the past few years, several small synthetic molecules that have an azaflavone nucleus as a core structure have been identified as tubulin inhibitors. Among these, several arylquinolinones, arylnaphthyridinones, arylquinazolinones and arylpyrroloquinolinones have shown to exert their anticancer activity through inhibition of tubulin polymerisation via the colchicine binding site. They arrest the cell growth at G2/M phase providing cell death via both mitotic and apoptotic pathway. Recently, some of them proved to be multi-inhibitor simultaneously targeting both PI3K-Akt-mTOR pathway and the microtubule cytoskeleton. Furthermore, some were demonstrated to possess effective anti-angiogenic properties similar to that of natural compounds combretastatine-A4 and vincristine. This article reviews the synthesis, biological activities and SARs of the main classes of azaflavones. Brief mention of the subtype 2- styrylquinazolinones has also been made.
authors.forename: Davide
authors.initials: D
authors.lastname: Carta
authors.affiliation: Department of Pharmaceutical and Pharmacological Sciences, Via Marzolo, 5, 35131 - Padova, Italy. mariagrazia.ferlin@unipd.it.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Ferlin
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008870:Microtubules / Q000187:drug effects*; D008938:Mitosis / Q000187:drug effects; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000473:pathology; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D009287:Naphthyridines; D052999:Quinazolinones; D015363:Quinolones; D050257:Tubulin Modulators; D003078:Colchicine