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Accordingly, several structural modifications mainly focused on the benzodioxole moiety were introduced, allowing us to gain new insights into the activity and biological profile. NCI antiproliferative screening (SRB colorimetric assay), together with MTS-based assay against six other tumour cell lines, enabled us a deeper understanding of the selectivity and potency patterns. This led to the identification of a new promising hit, compound 7p, which exhibited cytotoxic activity in the low micromolar range against MCF-7 and HeLa cells. Further biological evaluations, including apoptosis induction, clonogenic, and scratch tests, provided additional biological insights into the anticancer potential of these compounds, supporting the subsequent lead optimization process for more potent anticancer activity. The integrated in silico docking results evidenced a clear multi-target profile, as testified by the broad anticancer activity, and suggest a good potential for rational polypharmacology.<\/jats:p>","DOI":"10.3390\/biom15121718","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:39:18Z","timestamp":1765442358000},"page":"1718","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Tuning Scaffold Properties of New 1,4-Substituted Pyrrolo[3,2-c]quinoline Derivatives Endowed with Anticancer Potential, New Biological and In Silico Insights"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-4602","authenticated-orcid":false,"given":"Francesco","family":"Mingoia","sequence":"first","affiliation":[{"name":"Istituto per lo Studio dei Materiali Nanostrutturati (ISMN), Consiglio Nazionale delle Ricerche (CNR), Via U. 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