2‐Amino‐4‐aryl‐5‐oxo‐4, 5‐dihydropyrano[3, 2‐c]chromene‐3‐carbonitriles with Microtubule‐Disruptive, Centrosome‐Declustering, and Antiangiogenic Effects in vitro and in vivo. (16th March 2022)

• Record Type: Journal Article
• Authors: Köhler, Leonhard H. F.; Reich, Sebastian; Begemann, Gerrit; Schobert, Rainer; Biersack, Bernhard
• Is Part Of: ChemMedChem. Volume 17:Number 10(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-03-16
• Subjects: Pyrano[3, 2-c]chromene -- Centrosome de-clustering -- Antiangiogenic agents -- Anticancer drugs; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202200064
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: A series of fifteen 2‐amino‐4‐aryl‐5‐oxo‐4, 5‐dihydropyrano[3, 2‐ c ]chromene‐3‐carbonitriles (1 a –o ) were synthesized via a three‐component reaction of 4‐hydroxycoumarin, malononitrile, and diversely substituted benzaldehydes or pyridine carbaldehydes. The compounds were tested for anticancer activities against a panel of eight human tumor cell lines. A few derivatives with high antiproliferative activities and different cancer cell specificity were identified and investigated for their modes of action. They led to microtubule disruption, centrosome de‐clustering and G2/M cell cycle arrest in 518 A2 melanoma cells. They also showed anti‐angiogenic effects in vitro and in vivo . Abstract : De‐clustering cancer : A new 2‐amino‐4‐aryl‐5‐oxo‐4, 5‐dihydropyrano[3, 2‐ c ]chromene‐3‐carbonitrile with superior anticancer activity was identified. While selectively targeting cancer cells through centrosome de‐clustering, angiogenesis was significantly decreased in vitro and in vivo .