{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T05:28:27Z","timestamp":1771824507840,"version":"3.50.1"},"reference-count":29,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,26]],"date-time":"2022-08-26T00:00:00Z","timestamp":1661472000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Direct growth inhibition of infectious organisms coupled with immunomodulation to counteract the immunosuppressive environment might be a beneficial therapeutic approach. Herein, a library of sulfuretin analogs were developed with potential capabilities to inhibit production of the immunosuppressive PGE2 and elicit direct growth inhibition against Leishmania donovani; the major causative agent of the fatal visceral leishmaniasis. Amongst explored library members bearing diverse methoxy and\/or hydroxy substitution patterns at rings B and A, analog 1i retaining the C6-hydroxy moiety at ring-A, but possessing methoxy moieties in place of the polar dihydroxy moieties of sulfuretin ring-B, as well as analog 1q retaining the sulfuretin\u2032s polar dihydroxy moieties at ring-B, but incorporating a C6-methoxy moiety instead of the C6-hydroxy moiety at ring-A, were the most promising hit compounds. Cytotoxicity evaluation suggested that analog 1i possesses a safety profile inducing the death of the parasite rather than host cells. In silico simulation provided insights into their possible binding with Leishmania donovani fumarate reductase. The current investigation presents sulfuretin analogs 1i and 1q as potential hit compounds for further development of multifunctional therapeutic agents against visceral leishmaniasis.<\/jats:p>","DOI":"10.3390\/ph15091058","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T22:53:42Z","timestamp":1661813622000},"page":"1058","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Design, Rational Repurposing, Synthesis, In Vitro Evaluation, Homology Modeling and In Silico Study of Sulfuretin Analogs as Potential Antileishmanial Hit Compounds"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1048-6281","authenticated-orcid":false,"given":"Ahmed H.E.","family":"Hassan","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt"},{"name":"Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trong-Nhat","family":"Phan","sequence":"additional","affiliation":[{"name":"Host-Parasite Research Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeonwoo","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Fundamental Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suyeon","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Fundamental Pharmaceutical Sciences, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo Hwan","family":"No","sequence":"additional","affiliation":[{"name":"Host-Parasite Research Laboratory, Institut Pasteur Korea, Seongnam-si 13488, Gyeonggi-do, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6523-6979","authenticated-orcid":false,"given":"Yong Sup","family":"Lee","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry Laboratory, Department of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul 02447, Korea"},{"name":"Department of Life and Nanopharmaceutical Sciences, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13071-017-2028-5","article-title":"The history of leishmaniasis","volume":"10","author":"Steverding","year":"2017","journal-title":"Parasit. 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