{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T02:47:45Z","timestamp":1782096465887,"version":"3.54.5"},"reference-count":40,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100014787","name":"African Center of Excellence in Mathematics Computer Science and ICT","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014787","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,6,15]]},"abstract":"<jats:p>\n                    In this study, a bicyclic lactam derived from piperidine was synthesized via an asymmetric Michael reaction using a chiral imine\n                    <jats:bold>3<\/jats:bold>\n                    . In addition, twenty\u2010four nitrogen\u2010modulated analogues were synthesized, including 20 benzylated (\n                    <jats:bold>\n                      9a\u2013k(\n                      <jats:italic>S<\/jats:italic>\n                      )\n                    <\/jats:bold>\n                    and\n                    <jats:bold>\n                      ent\u20109a\u2013j(\n                      <jats:italic>R<\/jats:italic>\n                      )\n                    <\/jats:bold>\n                    ) and 4 acylated (\n                    <jats:bold>\n                      12(\n                      <jats:italic>S<\/jats:italic>\n                      )\n                    <\/jats:bold>\n                    and\n                    <jats:bold>\n                      13a\u2013c(\n                      <jats:italic>S<\/jats:italic>\n                      )\n                    <\/jats:bold>\n                    ) derivatives. All compounds were evaluated for their antileishmanial activity against axenic and intramacrophage amastigotes of\n                    <jats:italic>Leishmania major<\/jats:italic>\n                    (cutaneous leishmaniasis) and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    (visceral leishmaniasis). Several derivatives displayed potent activity with low toxicity toward macrophages and MRC\u20105 cell lines. Notably, compounds\n                    <jats:bold>ent\u20109b<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.33 and 0.78\u2009\u03bcM against intramacrophage amastigote forms of\n                    <jats:italic>L. major<\/jats:italic>\n                    and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    , respectively),\n                    <jats:bold>ent\u20109d<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.69 and 1.12\u2009\u03bcM),\n                    <jats:bold>ent\u20109e<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.21 and 0.43\u2009\u03bcM),\n                    <jats:bold>ent\u20109h<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.68 and 1.54\u2009\u03bcM), and\n                    <jats:bold>13b<\/jats:bold>\n                    (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.97 and 0.88 \u03bcM) exhibited remarkable activity and favorable selectivity indices compared with the reference drug miltefosine (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20092.74 and 1.03\u2009\u03bcM). Pharmacokinetic (ADME) analyses were conducted to assess their drug\u2010likeness and identify promising candidates for further development. Ligand\u2010based inverse virtual screening suggested\n                    <jats:italic>L. major<\/jats:italic>\n                    phosphodiesterase B1 and\n                    <jats:italic>L. donovani<\/jats:italic>\n                    cAMP\u2010specific phosphodiesterase as potential molecular targets. These compounds represent promising leads for further development in the fight against leishmaniasis.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70338","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T03:24:58Z","timestamp":1781148298000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bicyclic Lactams From Chiral Imines: Synthesis, Structural Optimization, and Biological Evaluation of Promising Antileishmanial Agents"],"prefix":"10.1002","volume":"21","author":[{"given":"Siga","family":"Sagne","sequence":"first","affiliation":[{"name":"Laboratoire de Chimie et Physique des Mat\u00e9riaux (LCPM) Universit\u00e9 Assane Seck de Ziguinchor  Ziguinchor Senegal"},{"name":"Cibles et m\u00e9dicaments des infections et de l\u2019immunit\u00e9 IICiMed UR 1155 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Cojean","sequence":"additional","affiliation":[{"name":"UMR BIPAR Laboratory of Animal Health, Anses, INRAe, EnvA  Maisons\u2010Alfort France"},{"name":"Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramata Ousmane","family":"Diallo","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Physique des Mat\u00e9riaux (LCPM) Universit\u00e9 Assane Seck de Ziguinchor  Ziguinchor Senegal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7685-9618","authenticated-orcid":false,"given":"Euz\u00e9bio G.","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Federal University of Rio Grande do Norte  Natal Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4823-5290","authenticated-orcid":false,"given":"Karen C.","family":"Weber","sequence":"additional","affiliation":[{"name":"Department of Chemistry Federal University of Para\u00edba  Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00edlia C.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Chemistry Federal University of Para\u00edba  Jo\u00e3o Pessoa Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oumar","family":"Sambou","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Physique des Mat\u00e9riaux (LCPM) Universit\u00e9 Assane Seck de Ziguinchor  Ziguinchor Senegal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Tomasoni","sequence":"additional","affiliation":[{"name":"Cibles et m\u00e9dicaments des infections et de l\u2019immunit\u00e9 IICiMed UR 1155 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justine","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Cibles et m\u00e9dicaments des infections et de l\u2019immunit\u00e9 IICiMed UR 1155 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Pagniez","sequence":"additional","affiliation":[{"name":"Cibles et m\u00e9dicaments des infections et de l\u2019immunit\u00e9 IICiMed UR 1155 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Cav\u00e9","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris\u2010Saclay  Gif\u2010sur\u2010Yvette France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdoulaye","family":"Gassama","sequence":"additional","affiliation":[{"name":"Laboratoire de Chimie et Physique des Mat\u00e9riaux (LCPM) Universit\u00e9 Assane Seck de Ziguinchor  Ziguinchor Senegal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7773-8642","authenticated-orcid":false,"given":"Pascal","family":"Marchand","sequence":"additional","affiliation":[{"name":"Cibles et m\u00e9dicaments des infections et de l\u2019immunit\u00e9 IICiMed UR 1155 Nantes Universit\u00e9  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"Leishmaniasis can be found under Available at:December 2025 https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/leishmaniasis."},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-021-07139-2"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens12020297"},{"key":"e_1_2_10_5_1","unstructured":"C.\u2010C for D. 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