Novel Thymohydroquinone Derivatives as Potential Anticancer Agents: Design, Synthesis, and Biological Screening
Ahmed H. Abdelazeem A B G , Yasser M. A. Mohamed A C , Ahmed M. Gouda A , Hany A. Omar D E and Majed M. Al Robaian FA Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
B Department of Pharmaceutical Chemistry, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia.
C Photochemistry Department, National Research Center, Dokki, Giza 12622, Egypt.
D Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab of Emirates.
E Department of Pharmacology, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt.
F Department of Pharmaceutics, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia.
G Corresponding author. Email: ahmed.abdelazeem@pharm.bsu.edu.eg; ahmed.pharm@yahoo.com
Australian Journal of Chemistry 69(11) 1277-1284 https://doi.org/10.1071/CH16102
Submitted: 23 February 2016 Accepted: 4 May 2016 Published: 7 June 2016
Abstract
The safety and efficacy of naturally occurring anticancer agents and their derivatives such as thymoquinone (TQ) and thymohydroquinone (THQ) have gained a rapidly growing interest. In an attempt to develop novel anticancer agents with superior activity, TQ was allowed to react with hydrazine hydrate, producing hydrazino thymohydroquinone 3. This new intermediate was subsequently reacted with various isocyanates, isothiocyanates, and acyl halides, affording three series of semicarbazone, semithiocarbazone, and acyl hydrazone derivatives, respectively. Subsequently, the anticancer activity of all the newly synthesised compounds against a panel of cancer cell lines was evaluated. Initial screening of the ability of the test compounds to inhibit cancer cell viability using the 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that compounds 5d and 6 exerted better activity against breast cancer than TQ, with half-maximal inhibitory concentration (IC50) values of 9.6 and 10.0 μM, respectively. MTT results were confirmed by the ability of these compounds to elicit apoptotic cell death through the activation of caspase 3/7 enzymes. Together, the present work provided a novel class of THQ-based derivatives with potent anticancer and apoptosis properties, thereby warranting further optimisation of these derivatives as novel members in cancer treatment protocols.
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