Chemical and Biological Evaluation of Novel 1-Chromeno[3,2-]pyridine Derivatives as MAO Inhibitors Endowed with Potential Anticancer Activity.

About twenty molecules sharing 1-chromeno[3,2-]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1-indol-3-yl fragments at C10, as well as a few small substituents at C6 and C8, were synthesized starting from 1,2,3,4-tetrahydro-2-methylchromeno[3,2-]pyridin-10-ones (1,2,3,4-THCP-10-ones, ) or 2,3-dihydro-2-methyl-1-chromeno[3,2-]pyridines (2,3-DHPCs, ). The newly synthesized compounds were tested as inhibitors of the human isoforms of monoamine oxidase (MAO A and B) and cholinesterase (AChE and BChE), and the following main SARs were inferred: (i) The 2,3-DHCP derivatives inhibit MAO A (IC about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one , bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC 0.51 μM) and moderate inhibitor of both ChEs (ICs 7-8 μM); (iii) the 1-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog achieving MAO B IC of 3.