{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:40:09Z","timestamp":1784227209287,"version":"3.55.0"},"reference-count":32,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"Ministry of Higher Education, Cameroon","award":["000000"],"award-info":[{"award-number":["000000"]}]},{"name":"Institut Pasteur Paris","award":["00000"],"award-info":[{"award-number":["00000"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:p>\n            Previous studies suggest that 3\u2032,5\u2032-dihydro-2\u2032H-spiro[indoline-3,1\u2032-isoquinolin]-2-ones (DSIIQs [spiroquindolones]) are multitarget antiplasmodial agents that combine the actions of spiroindolone and naphthylisoquinoline antimalarial agents. In this study, 12 analogues of compound (\u00b1)-5 (moxiquindole), the prototypical spiroquindolone, were synthesized and tested for antiplasmodial activity. Compound (\u00b1)-11 (a mixture of compounds 11a and 11b), the most potent analogue, displayed low-nanomolar activity against\n            <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n            chloroquine-sensitive 3D7 strain (50% inhibitory concentration [IC\n            <jats:sub>50<\/jats:sub>\n            ] for 3D7\u2009=\u200921\u2009\u00b1\u200902\u2009nM) and was active against all major erythrocytic stages of the parasite life cycle (ring, trophozoite, and schizont); it also inhibited hemoglobin metabolism and caused extensive vacuolation in parasites. In drug-resistant parasites, compound (\u00b1)-11 exhibited potent activity (IC\n            <jats:sub>50<\/jats:sub>\n            for Dd2\u2009=\u200958.34\u2009\u00b1\u20092.04\u2009nM) against the\n            <jats:named-content content-type=\"genus-species\">P. falciparum<\/jats:named-content>\n            multidrug-resistant Dd2 strain, and both compounds (\u00b1)-5 and (\u00b1)-11 displayed significant cross-resistance against the\n            <jats:italic>P. falciparum<\/jats:italic>\n            ATP4 mutant parasite Dd2 SJ733 but not against the Dd2 KAE609 strain.\n          <\/jats:p>","DOI":"10.1128\/aac.00607-22","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T14:04:00Z","timestamp":1669039440000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Spirofused Tetrahydroisoquinoline-Oxindole Hybrids (Spiroquindolones) as Potential Multitarget Antimalarial Agents: Preliminary Hit Optimization and Efficacy Evaluation in Mice"],"prefix":"10.1128","volume":"66","author":[{"given":"Noella M.","family":"Efange","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Buea, Buea, Southwest Region, Cameroon"},{"name":"Malaria Research Unit, Centre Pasteur du Cameroun, Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maloba M. M.","family":"Lobe","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Buea, Buea, Southwest Region, Cameroon"},{"name":"Institut de Recherches Medicales et d\u2019Etudes des Plantes Medicinales (IMPM), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauve R. T.","family":"Yamthe","sequence":"additional","affiliation":[{"name":"Institut de Recherches Medicales et d\u2019Etudes des Plantes Medicinales (IMPM), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeannette N. M.","family":"Pekam","sequence":"additional","affiliation":[{"name":"Malaria Research Unit, Centre Pasteur du Cameroun, Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Protus A.","family":"Tarkang","sequence":"additional","affiliation":[{"name":"Institut de Recherches Medicales et d\u2019Etudes des Plantes Medicinales (IMPM), Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-4832","authenticated-orcid":true,"given":"Lawrence","family":"Ayong","sequence":"additional","affiliation":[{"name":"Malaria Research Unit, Centre Pasteur du Cameroun, Yaound\u00e9, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M. N.","family":"Efange","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology, University of Buea, Buea, Southwest Region, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","unstructured":"World Health Organization. 2021. World malaria report 2021. https:\/\/www.who.int\/teams\/global-malaria-programme\/reports. 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