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

Kulikova, L.N.; Purgatorio, R.; Beloglazkin, A.A.; Tafeenko, V.A.; Reza, R.G.; Levickaya, D.D.; Sblano, S.; Boccarelli, A.; de Candia, M.; Catto, M.; Voskressensky, L.G.; Altomare, C.D.

Авторы: Kulikova Larisa N., Purgatorio Rosa, Beloglazkin Andrey A., Tafeenko Viktor A., Reza Raesi Gh, Levickaya Daria D., Sblano Sabina, Boccarelli Angelina, de Candia Modesto, Catto Marco, Voskressensky Leonid G., Altomare Cosimo D.
Журнал: International Journal of Molecular Sciences
Том: 24
Номер: 9
Год издания: 2023
Издательство: MDPI
Местоположение издательства: Basel, Switzerland
Первая страница: 7724
DOI: 10.3390/ijms24097724
Аннотация: first_pagesettingsOrder Article ReprintsOpen AccessArticleChemical and Biological Evaluation of Novel 1H-Chromeno[3,2-c]pyridine Derivatives as MAO Inhibitors Endowed with Potential Anticancer Activityby Larisa N. Kulikova 1,†ORCID,Rosa Purgatorio 2,†ORCID,Andrey A. Beloglazkin 3,Viktor A. Tafeenko 4ORCID,Raesi Gh. Reza 1,Daria D. Levickaya 1ORCID,Sabina Sblano 2ORCID,Angelina Boccarelli 5ORCID,Modesto de Candia 2ORCID,Marco Catto 2ORCID,Leonid G. Voskressensky 1ORCID andCosimo D. Altomare 2,*ORCID1Organic Chemistry Department, Peoples’ Friendship University of Russia (RUDN University), 6 Miklukho-Maklaya St., 117198 Moscow, Russia2Department of Pharmacy-Pharmaceutical Sciences, University of Bari Aldo Moro, Via E. Orabona 4, 70125 Bari, Italy3A.V. Topchiev Institute of Petrochemical Synthesis, Russian Academy of Sciences, 29 Leninskiy Prosp., 119991 Moscow, Russia4Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119234 Moscow, Russia5Department of Precision and Regenerative Medicine and Ionian Area, School of Medicine, University of Bari Aldo Moro, Piazza Giulio Cesare 11, 70124 Bari, Italy*Author to whom correspondence should be addressed.†These authors contributed equally to this work.Int. J. Mol. Sci. 2023, 24(9), 7724; https://doi.org/10.3390/ijms24097724Received: 28 March 2023 / Revised: 13 April 2023 / Accepted: 17 April 2023 / Published: 23 April 2023(This article belongs to the Special Issue Enzymes and Enzyme Inhibitors—Applications in Medicine and Diagnosis 2.0)Download Browse Figures Review Reports Versions NotesAbstractAbout twenty molecules sharing 1H-chromeno[3,2-c]pyridine as the scaffold and differing in the degree of saturation of the pyridine ring, oxidation at C10, 1-phenylethynyl at C1 and 1H-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-c]pyridin-10-ones (1,2,3,4-THCP-10-ones, 1) or 2,3-dihydro-2-methyl-1H-chromeno[3,2-c]pyridines (2,3-DHPCs, 2). 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 2 inhibit MAO A (IC50 about 1 μM) preferentially; (ii) the 1,2,3,4-THCP-10-one 3a, bearing the phenylethynyl fragment at C1, returned as a potent MAO B inhibitor (IC50 0.51 μM) and moderate inhibitor of both ChEs (IC50s 7–8 μM); (iii) the 1H-indol-3-yl fragment at C10 slightly increases the MAO B inhibition potency, with the analog 6c achieving MAO B IC50 of 3.51 μM. The MAO B inhibitor 3a deserves further pharmacological studies as a remedy in the symptomatic treatment of Parkinson’s disease and neuroprotectant for Alzheimer’s disease. Besides the established neuroprotective effects of MAO inhibitors, the role of MAOs in tumor insurgence and progression has been recently reported. Herein, antiproliferative assays with breast (MCF-7), colon (HCT116) and cisplatin-resistant ovarian (SK-OV-3) tumor cells revealed that the 10-indolyl-bearing 2,3,4,10-THCP analog 6c exerts anti-tumor activity with IC50s in the range 4.83–11.3 μM.
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Chemical and Biological Evaluation of Novel 1H-Chromeno[3,2-c]pyridine Derivatives as MAO Inhibitors Endowed with Potential Anticancer Activityстатья

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