Synthesis of new antiproliferative 1,3,4-substituted-pyrrolo[3,2-c]quinoline derivatives, biological and in silico insights.

Publication date: Oct 05, 2023

A series of biologically unexplored substituted 1,3,4-subtituted-pyrrolo[3,2-c]quinoline derivatives (PQs) was evaluated against a panel of about 60 tumor cells (NCI). Based on the preliminary antiproliferative data, the optimizations efforts permitted us to design and synthesize a new series of derivatives allowing us to individuate a promising hit (4g). The insertion of a 4-benzo[d] [1,3]dioxol-5-yl moiety on increased and extended the activity towards five panel tumor cell lines such as leukemia, CNS, melanoma, renal and breast cancer, reaching IG in the low μM range. Replacement of this latter with a 4-(OH-di-Cl-Ph) group (4i) or introduction a Cl-propyl chain in position 1 (5), selectively addressed the activity against the entire leukemia sub-panel (CCRF-CEM, K-562, MOLT-4, RPMI-8226, SR). Preliminary biological assays on MCF-7 such as cell cycle, clonogenic assay, ROS content test alongside a comparison of viability between MCF-7 and non-tumorigenic MCF-10 were investigated. Among the main anticancer targets involved in breast cancer, HSP90 and ER receptors were selected for in silico studies. Docking analysis revealed a valuable affinity for HSP90 providing structural insights on the binding mode, and useful features for optimization.

Concepts Keywords
13dioxol Antiproliferative
4i Breast cancer
Antiproliferative Docking
Cancer HSP90
Hsp90 Pyrrolo[3,2-c]quinoline


Type Source Name
disease MESH tumor
disease MESH leukemia
disease MESH melanoma
pathway KEGG Melanoma
disease MESH breast cancer
pathway KEGG Breast cancer
pathway KEGG Cell cycle

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