title: Structural simplification of bioactive natural products with multicomponent synthesis. 2. antiproliferative and antitubulin activities of pyrano[3,2-c]pyridones and pyrano[3,2-c]quinolones.
abstract: Pyrano[3,2- c]pyridone and pyrano[3,2- c]quinolone structural motifs are commonly found in alkaloids manifesting diverse biological activities. As part of a program aimed at structural simplification of bioactive natural products utilizing multicomponent synthetic processes, we developed compound libraries based on these privileged heterocyclic scaffolds. The selected library members display low nanomolar antiproliferative activity and induce apoptosis in human cancer cell lines. Mechanistic studies reveal that these compounds induce cell cycle arrest in the G2/M phase and block in vitro tubulin polymerization. Because of the successful clinical use of microtubule-targeting agents, these heterocyclic libraries are expected to provide promising new leads in anticancer drug design.
authors: Department of Chemistry, New Mexico Institute of Mining and Technology, Socorro, New Mexico 87801, USA. imagedov@gmail.com
authors: Igor V
authors: IV
authors: Magedov
authors: Madhuri
authors: M
authors: Manpadi
authors: Marcia A
authors: MA
authors: Ogasawara
authors: Adriana S
authors: AS
authors: Dhawan
authors: Snezna
authors: S
authors: Rogelj
authors: Severine
authors: S
authors: Van Slambrouck
authors: Wim F A
authors: WF
authors: Steelant
authors: Nikolai M
authors: NM
authors: Evdokimov
authors: Pavel Y
authors: PY
authors: Uglinskii
authors: Eerik M
authors: EM
authors: Elias
authors: Erica J
authors: EJ
authors: Knee
authors: Paul
authors: P
authors: Tongwa
authors: Mikhail Yu
authors: MY
authors: Antipin
authors: Alexander
authors: A
authors: Kornienko
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011728:Pyridones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014404:Tubulin / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D011728:Pyridones; D015363:Quinolones; D014404:Tubulin