Abstract

Antiproliferative activity of pyrrolo[3,4-d]isoxazolines and pyrrolo[2,1-a]isoquinolines derived from them was studied against human erythroleukemia (K562), cervical carcinoma (HeLa), and melanoma (Sk-mel-2) cell lines in vitro by MTS assays followed by study of their effect on actin cytoskeleton and cell motility by confocal microscopy, and apoptotic activity by flow cytometry. Most effective among the screened compounds were bicyclic hydroxylactams 6–9 with a pyrrolo[3,4-d]isoxazoline structure; they showed IC50 values ranging from 12 to 36 μg/mL for all tested cancer cell lines with selectivity indexes up to 12 (as compared to the embryonic kidney HEK293T cell line). Loss of stress fibers with diffuse redistribution of granular actin throughout the cytoplasm in up to 25% of treated cells and a decrease in filopodia-like protrusions up to 69% were observed by confocal microscopy during an actin cytoskeleton study. Such cytoskeletal changes and the proposed altered cell motility were confirmed by scratch-test (revealed a three-fold decrease in cell motility).

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