{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:25:24Z","timestamp":1789608324970,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"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>Linearolactone (LL) is a neo-clerodane type diterpene that has been shown to exert giardicidal effects; however, its mechanism of action is unknown. This work analyzes the cytotoxic effect of LL on Giardia intestinalis trophozoites and identifies proteins that could be targeted by this active natural product. Increasing concentrations of LL and albendazole (ABZ) were used as test and reference drugs, respectively. Cell cycle progression, determination of reactive oxygen species (ROS) and apoptosis\/necrosis events were evaluated by flow cytometry (FCM). Ultrastructural alterations were analyzed by transmission electron microscopy (TEM). Ligand\u2013protein docking analyses were carried out using the LL structure raised from a drug library and the crystal structure of an aldose reductase homologue (GdAldRed) from G. intestinalis. LL induced partial arrest at the S phase of trophozoite cell cycle without evidence of ROS production. LL induced pronecrotic death in addition to inducing ultrastructural alterations as changes in vacuole abundances, appearance of perinuclear and periplasmic spaces, and deposition of glycogen granules. On the other hand, the in silico study predicted that GdAldRed is a likely target of LL because it showed a favored change in Gibbs free energy for this complex.<\/jats:p>","DOI":"10.3390\/ph15070809","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T22:43:28Z","timestamp":1656542608000},"page":"809","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Linearolactone Induces Necrotic-like Death in Giardia intestinalis Trophozoites: Prediction of a Likely Target"],"prefix":"10.3390","volume":"15","author":[{"given":"Ra\u00fal","family":"Arg\u00fcello-Garc\u00eda","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica y Biolog\u00eda Molecular, Centro de Investigaci\u00f3n y Estudios Avanzados, IPN, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1851-5988","authenticated-orcid":false,"given":"Fernando","family":"Calzada","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Farmacolog\u00eda, 2\u00b0 Piso CORCE, UMAE Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Av. Cuauht\u00e9moc 330, Colonia Doctores, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bibiana","family":"Ch\u00e1vez-Mungu\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Infect\u00f3mica y Patog\u00e9nesis Molecular, CINVESTAV-IPN, Av. Instituto Polit\u00e9cnico Nacional No. 2508, Colonia San Pedro Zacatenco, Mexico City 07360, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audif\u00e1s-Salvador","family":"Matus-Meza","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, 985830 Nebraska Medical Center, Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7050-9182","authenticated-orcid":false,"given":"Elih\u00fa","family":"Bautista","sequence":"additional","affiliation":[{"name":"CONACyT-Divisi\u00f3n de Biolog\u00eda Molecular, Instituto Potosino de Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica A. C., San Luis Potos\u00ed 78216, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7111-7922","authenticated-orcid":false,"given":"Elizabeth","family":"Barbosa","sequence":"additional","affiliation":[{"name":"Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Salvador D\u00edaz Mir\u00f3n Esq. Plan de San Luis S\/N, Miguel Hidalgo, Casco de Santo Tomas, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Velazquez","sequence":"additional","affiliation":[{"name":"\u00c1rea Acad\u00e9mica de Farmacia, Instituto de Ciencias de la Salud, Universidad Aut\u00f3noma del Estado de Hidalgo, Km 4.5, Carretera Pachuca-Tulancingo, Unidad Universitaria, Pachuca 42076, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-2118","authenticated-orcid":false,"given":"Marta Elena","family":"Hern\u00e1ndez-Caballero","sequence":"additional","affiliation":[{"name":"Facultad de Medicina, Biomedicina, Benem\u00e9rita Universidad Aut\u00f3noma de Puebla, Puebla 72410, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-9175","authenticated-orcid":false,"given":"Rosa Maria","family":"Ordo\u00f1ez-Razo","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n M\u00e9dica en Gen\u00e9tica Humana, UMAE Hospital de Pediatr\u00eda 2\u00b0 Piso, Centro M\u00e9ddico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauht\u00e9moc 330, Colonia Doctores, Mexico City 06725, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4504-8166","authenticated-orcid":false,"given":"Jos\u00e9 Antonio","family":"Vel\u00e1zquez-Dom\u00ednguez","sequence":"additional","affiliation":[{"name":"Escuela Nacional de Medicina y Homeopat\u00eda IPN, Av. Guillermo Massieu Helguera, No. 239, La Escalera, Mexico City 07320, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","unstructured":"Biagi, F. (1980). Giardiasis, Enfermedades Parasitarias, La Prensa Mexicana. 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