Novel R-(+)-limonene-based thiosemicarbazones and their antitumor activity against human tumor cell lines

•Synthesis of 19 new thiosemicarbazones containing the natural monoterpene R-(+)-limonene linked to N-4 position.•Antitumoral activity screening against ten human cancer cell lines.•The majority of synthesized compounds were sensitive to prostate cells PC-3.•Derivative p-fluorothiosemicarbazone 10 was the most selective compound against PC-3 cell.•Derivative o-hydroxythiosemicarbazone 8 was the most active compound against all tested tumor cell lines.

In an attempt to develop potent and selective antitumor agents, a series of novel thiosemicarbazones derived from a natural monoterpene R-(+)-limonene was synthesized and their antitumor activity was evaluated. Overall, the majority of tested compounds exhibited considerable inhibitory effects on the growth of a wide range of cancer cell lines. Almost all of tested thiosemicarbazones were especially sensitive to prostate cells (PC-3). Derivatives 5, 6, 8, 9, 10, 11 and 13 presented the most potent antitumor activity against PC-3 cells. These compounds showed lower value of GI50 (0.04–0.05 μM) than the reference drug paclitaxel, besides a high selectivity for the same cell line. The 4-fluorobenzaldehyde derivative 10 was the most selective compound for prostate cells, while 2-hydroxybenzaldehyde derivative 8 was the most active compound, with potent antitumor activity against all tested cell lines.

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