Thiazolation of phenylthiosemicarbazone to access new thiazoles: anticancer activity and molecular docking

Abstract

<b>Aim:</b> Novel thiazole hybrids were synthesized via thiazolation of 4-phenylthiosemicarbazone (<b>4</b>). <b>Materials & methods:</b> The anticancer activity against the NCI 60 cancer cell line panel. <b>Results:</b> Methyl 2-(2-((1-(naphthalen-2-yl)ethylidene)hydrazineylidene)-4-oxo-3-phenylthiazolidin-5-ylidene)acetate (<b>6a</b>) showed significant anticancer activity at 10 μM with a mean growth inhibition (GI) of 51.18%. It showed the highest cytotoxic activity against the ovarian cancer OVCAR-4 with an IC₅₀ of 1.569 ± 0.06 μM. Compound <b>6a</b> inhibited PI3Kα with IC₅₀ = 0.225 ± 0.01 μM. Moreover, compound <b>6a</b> revealed a decrease of Akt and mTOR phosphorylation in OVCAR-4 cells. In addition, antibacterial activity showed that compounds <b>11</b> and <b>12</b> were the most active against <i>Staphylococcus aureus</i>. <b>Conclusion:</b> Compound <b>6a</b> is a promising molecule that could be a lead candidate for further studies.