Synthesis and evaluation of anticancer activity of pyrrolo[3,4-d]isoxazoles against tumor cell lines

Oncological diseases represent a major global health challenge and are the second leading cause of mortality. The discovery of novel chemotherapeutic agents with improved efficacy and safety profiles remains a critical objective in medicinal chemistry. In this pursuit, heterocyclic compounds serve as privileged structures in drug design. Isoxazole derivatives, in particular, are recognized as a prime scaffold due to their remarkable ability to interact with diverse biological targets, demonstrating a broad spectrum of pharmacological activities.

This work focuses on the design, synthesis, and biological evaluation of a new series of heterocyclic compounds incorporating the synthetically versatile pyrrolo[3,4-d]isoxazole framework. The synthesized novel derivatives were screened for their in vitro antiproliferative activity against three human cancer cell lines: cervical carcinoma (HeLa), erythroleukemia (K-562), and melanoma (Sk-mel-2). The results revealed that several adducts exhibited significant cytotoxic effects, with half-maximal inhibitory concentration (IC₅₀) values as potent as 15 μg/mL.

To gain insight into the potential mechanism of action, a confocal microscopy analysis was conducted. Treatment with the active compounds induced pronounced cytoskeletal alterations, specifically a diffuse redistribution of granular actin within the cytoplasm concomitant with the disappearance of structured actin filaments. A notable reduction in filopodia-like membrane protrusions was also observed. These findings collectively substantiate the promising antitumor potential of the synthesized pyrrolo[3,4-d]isoxazole derivatives, warranting further investigation into their therapeutic applications.