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.

A Convenient and Efficient Method for the Synthesis of a Novel Series of N‑Butyl‑1,4-oxazino[2’,3’:4,5]pyrano[3,2-c]quinolinones

“…12 Pyrano[3,2-c]quinolinones skeletons, including both quinolone ring and pyran moiety, have received much attention due to their various biological properties. [13][14][15][16] Despite this extensive body of published work on the biological activities of these two types of heterocycles, we did not find any literature reports pointing to the heteroannulation of an oxazine nucleus with the pyranoquinolone moiety in one fused molecular frame. Rings annulated to the pyranoquinolinone units showed potential medicinal properties such as antibacterial, 17 anticoagulant, 18 antitumor, 19 and microtubule-targeting agents.…”

“…Rings annulated to the pyranoquinolinone units showed potential medicinal properties such as antibacterial, 17 anticoagulant, 18 antitumor, 19 and microtubule-targeting agents. 14 Prompted by the encouraging literature precedent we embarked on the synthesis of this fused heteroannulated system. We recently reported the preparation of synthetically valuable 3-amino-4-hydroxypyranoquinolinone (1) as a versatile precursor for hetrocyclization reaction of pyranoquinolinone.…”

Nano-sawdust–BF3 as a new, cheap, and effective nano catalyst for one-pot synthesis of 2-amino benzo[h]chromene derivatives

“…2-amino benzo [h]chromene are some examples of multi-component reactions. 4H-chromenes and fused 4H-chromene derivatives are attractive, because they generally show biological properties such as anti-microbial, anti-oxidant, anti-tumor, hypotensive and antiproliferation activities [2][3][4][5][6].…”

Nucleophilic substitution and ring transformation reactions with 4-chloro-6-ethyl-3-nitropyrano[3,2-c]quinoline-2,5(6H)-dione

“…For example, some quinolinones are recently reported to have potential as inhibitors for hepatitis C polymerase, 1,2 microsomal prostaglandin E 2 synthase-1 3 and selective iNOS 4 . Many quinolinone derivatives have been found active as antimalarial parasite agents, 5 antiamebics, and antischistosomal agents, [6][7][8] and to have antibacterial, 9,10 antiproliferative and antitubulin, 11 anti-hepatitis B virus (HBV) 12,13 anti-HIV-1 14 activities.…”