Reaction of nucleophilic active phosphacumulenes with iso(thio)cyanates were performed. Novel heterocyclic four-membered or six-membered compounds containing sulfur and nitrogen nucleus namely, thietane, azetidine and thiazinane were prepared. Moreover, the thiocarbamoyl derivatives were produced from the reaction of the stable phosphonium ylides with the iso(thio)cyanate derivatives. Besides the cytotoxic activity of iso(thio)cyanate derivatives and some new organophosphorus compounds were determined, using MTT assay against human HepG2 hepatocellular carcinoma and MCF-7 adenocarcinoma breast cancer cell lines in comparison with the activity of the known anticancer drug 5-flurouracil as a reference drug. All the tested compounds showed concentration dependent increase in the growth inhibition percentage against HepG2 and MCF-7 cancer cell lines. Moreover, the synthesized thietanes and thiazinanes revealed anticancer activity with IC50 (20, 8.9, 12.7, 32.5 µg/mL) respectively against HepG2 and (20, 10.3, 20 and 20 µg/mL) respectively against MCF-7 cancer cell lines. The newly synthesized azetidines showed anticancer activity with IC50 (13.5 and 32.5 µg/mL) against HepG2 and IC50 (10 and 25.9 µg/mL) against MCF-7 cancer cell lines. Moreover, azetidinedione compound exhibited more potent activity than the azetidinone with both types of cancer cell lines. In addition the cytotoxic activity of the iso(thio)cyanates , and malonamic acid methyl ester compounds were also investigated. 4-Methoxyphenylisothiocyanate and methylisothiocyanate, with IC50 (25.9, 12.3 and 40, 20 µg/mL) respectively against HepG2 and MCF-7 cancer cells were reported. 1,2-Dichloro-4-isocyanatobenzene was simillar in potency to the known anticancer drug 5-flurouracil with IC50 (5.3 µg/mL) versus 5 µg/mL for 5-flurouracil against MCF-7. While, malonamic acid methyl ester compound had no effect on both types of cancer cell lines.
Key words: Human HepG2, MCF-7 cancer cells, cytotoxic activity, 5-flurouracil, iso(thio)cyanates, and organophosphorus compounds
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