{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:38:39Z","timestamp":1792805919431,"version":"4.5.0"},"reference-count":47,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T00:00:00Z","timestamp":1530662400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5G12MD007592"],"award-info":[{"award-number":["5G12MD007592"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R25GM069621-11"],"award-info":[{"award-number":["R25GM069621-11"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Lung Cancer Research Foundation and the Green Fund","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"https:\/\/ror.org\/00f7y2s26","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["HRD-1202008"],"award-info":[{"award-number":["HRD-1202008"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the National Institutes of Science and Technology (INCT-IDN, Brazil) Science Without Borders Program\/CNPq","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"https:\/\/ror.org\/052a22698","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Leishmania major (L. major) is a protozoan parasite that causes cutaneous leishmaniasis. About 12 million people are currently infected with an annual incidence of 1.3 million cases. The purpose of this study was to synthesize a small library of novel thiophene derivatives, and evaluate its parasitic activity, and potential mechanism of action (MOA). We developed a structure\u2013activity relationship (SAR) study of the thiophene molecule 5A. Overall, eight thiophene derivatives of 5A were synthesized and purified by silica gel column chromatography. Of these eight analogs, the molecule 5D showed the highest in vitro activity against Leishmania major promastigotes (EC50 0.09 \u00b1 0.02 \u00b5M), with an inhibition of the proliferation of intracellular amastigotes higher than 75% at only 0.63 \u00b5M and an excellent selective index. Moreover, the effect of 5D on L. major promastigotes was associated with generation of reactive oxygen species (ROS), and in silico docking studies suggested that 5D may play a role in inhibiting trypanothione reductase. In summary, the combined SAR study and the in vitro evaluation of 5A derivatives allowed the identification of the novel molecule 5D, which exhibited potent in vitro anti-leishmanial activity resulting in ROS production leading to cell death with no significant cytotoxicity towards mammalian cells.<\/jats:p>","DOI":"10.3390\/molecules23071626","type":"journal-article","created":{"date-parts":[[2018,7,4]],"date-time":"2018-07-04T12:23:02Z","timestamp":1530706982000},"page":"1626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Development of Thiophene Compounds as Potent Chemotherapies for the Treatment of Cutaneous Leishmaniasis Caused by Leishmania major"],"prefix":"10.3390","volume":"23","author":[{"given":"Felipe","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Iniguez","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guadalupe","family":"Pena Contreras","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidar","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8408-7355","authenticated-orcid":false,"given":"Thadeu E. M. M.","family":"Costa","sequence":"additional","affiliation":[{"name":"Centro de Desenvolvimento Tecnol\u00f3gico em Sa\u00fade, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ 21040-361, Brazil"},{"name":"Instituto de Tecnologia em F\u00e1rmacos-Farmanguinhos, Funda\u00e7\u00e3o Oswaldo Cruz, Rio de Janeiro, RJ 22775-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachid","family":"Skouta","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Department of Chemistry, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"},{"name":"Department of Biology, University of Massachusetts, Amherst, MA 01003-9297, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa A.","family":"Maldonado","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Border Biomedical Research Center, The University of Texas at El Paso, El Paso, TX 79968, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alvar, J., Velez, I.D., Bern, C., Herrero, M., Desjeux, P., Cano, J., Jannin, J., den Boer, M., and WHO Leishmaniasis Control Team (2012). 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