SEMISYNTHESIS OF SOME NOVEL THIOUREA AND CARBAMIMIDOTHIOIC ACID DERIVATIVES USING NATURAL ALKALOID L-NOREPHEDRINE AND THEIR ANTICANCER ACTIVITY

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*Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451 Kingdom of Saudi Arabia;
**Department of Drug Radiation Research, National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 29 Nasr City, Cairo, Egypt;
***Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin AbdulAziz University, P.O. Box 173, Al-Kharj, 11942 Kingdom of Saudi Arabia;
****Department of Pharmacognosy, College of Pharmacy, Alexandria University, Alexandria, 21215 Egypt

Received November 18, 2015; in final form, April 11, 2016

DOI: 10.7868/S0132342316050110

A novel series of thiourea and carbamimidothioic acid derivatives was synthesized using natural alkaloid L-norephedrine as a starting material. Structures of the newly synthesized compounds were confirmed by analytical and spectral data. The synthesized compounds were evaluated in vitro for anticancer activity against the human breast (MCF-7), human liver (HEPG2), and human colon (HCT116) cancer cell lines. Best activity of the synthesized compounds was expressed against HEPG2, however, none of the compounds exceeded the IC₅₀ of doxorubicin. The corresponding N-(1-(2-chloroacetoxy)-1-phenylpropan-2-yl)-N'-p-tolylcarbamimidothioic acid was the most potent compound and exhibited higher cytotoxic activity against the human colon cancer cell line (HCT116) when compared with the reference drug doxorubicin. Also, this compound was the most active against the MCF-7 cell line but less active than the positive control.

Keywords: thiourea, carbamimidothioic acid derivatives, L-norephedrine, anticancer activity.

Биоорг. химия 2016, 42 (5): 624-630