{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T02:45:53Z","timestamp":1769222753738,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>To further extend the structure\u2013activity relationships on previously identified anti-proliferative imidazo-pyrazoles, a novel series of compounds was designed and synthesized. In the obtained derivatives (1), the imidazo-pyrazole scaffold was formally condensed with a substituted triazole moiety, known for its biological properties. All derivatives were tested for anti-proliferative activity on a panel of 60 different cancer cell lines and compound 1h was identified as the most promising derivative, being highly effective against melanoma cells. Additional investigations demonstrated a cytotoxic and pro-oxidant action of the compound 1h on human metastatic melanoma cell lines (MeOV and MeTA) but not on healthy keratinocytes (HaCAT), confirming the selective activity of the compound. In silico calculations predicted favorable drug-like and pharmacokinetic properties and pre-formulation studies evaluated the effect of Tween 80 on 1h solubility. Overall, the collected data confirmed the pharmacological potential of the imidazo-pyrazole scaffold and indicated 1h as an interesting lead structure for the development of novel anti-melanoma agents.<\/jats:p>","DOI":"10.3390\/ijms26136312","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T06:56:54Z","timestamp":1751353014000},"page":"6312","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Triazole-imidazo[1,2-b]pyrazoles Able to Counteract Melanoma Cell Survival Without Compromising the Viability of Healthy Keratinocytes"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2575-7726","authenticated-orcid":false,"given":"Chiara","family":"Brullo","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3056-6569","authenticated-orcid":false,"given":"Barbara","family":"Marengo","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, Via Leon Battista Alberti 2, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"},{"name":"Centro 3R, Department of Information Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5003-7333","authenticated-orcid":false,"given":"Cinzia","family":"Domenicotti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine (DIMES), University of Genova, Via Leon Battista Alberti 2, 16132 Genoa, Italy"},{"name":"IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132 Genoa, Italy"},{"name":"Centro 3R, Department of Information Engineering, University of Pisa, Largo Lucio Lazzarino 1, 56122 Pisa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-7891","authenticated-orcid":false,"given":"Matteo","family":"Lusardi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Cichero","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3082-2908","authenticated-orcid":false,"given":"Annalisa","family":"Salis","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicines, University of Genoa, Viale Benedetto XV 1, 16132 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debora","family":"Caviglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5856-7929","authenticated-orcid":false,"given":"Eleonora","family":"Russo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3360-7146","authenticated-orcid":false,"given":"Andrea","family":"Spallarossa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1007\/s00044-013-0887-7","article-title":"New 6-bromoimidazo [1,2-a]pyridine-2-carbohydrazide derivatives: Synthesis and anticonvulsant studies","volume":"23","author":"Ulloora","year":"2014","journal-title":"Med. 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