Spirochromanone Cst-17 as a potent microtubule destabilizing agent showing anticancer effects in HeLa cells by...

To unravel the cytotoxic behavior of spirochromanone against the HeLa cell line and to evaluate its potential as a microtubule-targeting agent (MTA).

21 synthetic analogues of spiro[chroman-2,4'-piperidin]-4-one hydrochloride were screened for their cytotoxic effect on human cervical carcinoma cell line (HeLa), lung adenocarcinoma cell line (A549), and human embryonic kidney cell line (HEK-293). For cellular experiments, HeLa cells was used and tubulin interaction studies were conducted using tissue purified tubulin. An in silico assay was done for binding site determination, and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis was performed to evaluate the drug-likeness.

Among the 21 synthetic compounds, Cst-17 showed potential anticancer effect. Cst-17 had nearly equal cytotoxicity against both HeLa and A549 cells (IC₅₀ values of 9.03 ± 1.13 µM and 9.33 ± 0.60 µM, respectively). It disrupted the interphase microtubule network, arrested HeLa cells at G2/M phase, altered mitochondrial membrane potential (MMP) and induced caspase-dependent apoptosis. Cst-17 triggered microtubule destabilization (IC₅₀ ~ 16 ± 4 µM) on binding near the colchicine-binding site (K_d = 10.98 ± 1.32 μM). ADMET analysis revealed the promising pharmacokinetic properties of Cst-17.

Cst-17 is a potential MTA that triggers apoptosis by arresting HeLa cells at G2/M phase.