A New Naphthopyran Derivative Combines -Myb Inhibition, Microtubule-Targeting Effects, and Antiangiogenic Properties

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2022 Nov 17

PMID 36385941

Authors

Leonhard H F Kohler

Sebastian Reich

Maria Yusenko

Karl-Heinz Klempnauer

Amin H Shaikh

Khursheed Ahmed

Gerrit Begemann

Rainer Schobert

Bernhard Biersack

Affiliations

Soon will be listed here.

Abstract

Based on the promising -Myb inhibitor , a series of 2-amino-4-aryl-4-naphtho[1,2-]pyran-3-carbonitriles (, -, -) were repurposed or newly synthesized via a three-component reaction of 1-naphthol, and various aryl aldehydes and malononitrile and screened for their -Myb inhibitory activities. also served as a lead compound for seven new naphthopyran derivatives (-), which were cytotoxic with nanomolar IC values, to inhibit the polymerization of tubulin, and to destabilize microtubules in living cells. Especially, the alkyne , originally made for intracellular localization studies using click chemistry, showed an overall high activity in all assays performed. A strong G2/M cell cycle arrest was detected, which resulted in a distinct increase in sub-G1 cells through the induction of effector caspases 3 and 7. Inhibition of angiogenesis was confirmed and . In summary, was found to be a pleiotropic compound with high selectivity for cancer cells, combining Myb inhibitory, microtubule destabilizing, and antiangiogenic effects.

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