{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T20:57:31Z","timestamp":1771707451492,"version":"3.50.1"},"reference-count":77,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"U.S. Army Medical Research and Material Command (USAMRMC)","award":["W81XWH1820029"],"award-info":[{"award-number":["W81XWH1820029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>8-Aminoquinolines (8-AQs) are an important class of anti-infective therapeutics. The monoamine oxidases (MAOs) play a key role in metabolism of 8-AQs. A major role for MAO-A in metabolism of primaquine (PQ), the prototypical 8-AQ antimalarial, has been demonstrated. These investigations were further extended to characterize the enantioselective interactions of PQ and NPC1161 (8-[(4-amino-1-methylbutyl) amino]-5-[3, 4-dichlorophenoxy]-6-methoxy-4-methylquinoline) with human MAO-A and -B. NPC1161B, the (R)-(\u2212) enantiomer with outstanding potential for malaria radical cure, treatment of visceral leishmaniasis and pneumocystis pneumonia infections is poised for clinical development. PQ showed moderate inhibition of human MAO-A and -B. Racemic PQ and (R)-(\u2212)-PQ both showed marginally greater (1.2- and 1.6-fold, respectively) inhibition of MAO-A as compared to MAO-B. However, (S)-(+)-PQ showed a reverse selectivity with greater inhibition of MAO-B than MAO-A. Racemic NPC1161 was a strong inhibitor of MAOs with 3.7-fold selectivity against MAO-B compared to MAO-A. The (S)-(+) enantiomer (NPC1161A) was a better inhibitor of MAO-A and -B compared to the (R)-(\u2212) enantiomer (NPC1161B), with more than 10-fold selectivity for inhibition of MAO-B over MAO-A. The enantioselective interaction of NPC1161 and strong binding of NPC1161A with MAO-B was further confirmed by enzyme-inhibitor binding and computational docking analyses. Differential interactions of PQ and NPC1161 enantiomers with human MAOs may contribute to the enantioselective pharmacodynamics and toxicity of anti-infective 8-AQs therapeutics.<\/jats:p>","DOI":"10.3390\/ph14050398","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"398","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enantioselective Interactions of Anti-Infective 8-Aminoquinoline Therapeutics with Human Monoamine Oxidases A and B"],"prefix":"10.3390","volume":"14","author":[{"given":"Narayan D.","family":"Chaurasiya","sequence":"first","affiliation":[{"name":"Division of Drug Discovery, Department of Infectious Diseases, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haining","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Bio-Molecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3789-1842","authenticated-orcid":false,"given":"Robert J.","family":"Doerksen","sequence":"additional","affiliation":[{"name":"Department of Bio-Molecular Sciences, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA"},{"name":"National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. P. Dhammika","family":"Nanayakkara","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry A.","family":"Walker","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4545-4316","authenticated-orcid":false,"given":"Babu L.","family":"Tekwani","sequence":"additional","affiliation":[{"name":"Division of Drug Discovery, Department of Infectious Diseases, Southern Research, Birmingham, AL 35205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s11908-019-0698-1","article-title":"Utility of 8-Aminoquinolines in Malaria Prophylaxis in Travelers","volume":"21","author":"Meltzer","year":"2019","journal-title":"Curr. 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