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Design, Docking Studies, and Anticancer Activity of Newly Synthesized Monastrol Analogues Bearing Ligustrazine Moiety

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Abstract

In order to produce new anti-cancer medications with various effects and minimum toxicity, a series of monastrol derivatives was synthesized by employing many potent anti-tumor aspects of ligustrazine derivatives as starting materials. The “combination principle” in drug discovery enlightened our thinking. Thus, the design and synthesis of monastrol analogues bearing ligustrazine moiety was achieved by the reaction of 2-thioxopyrimidine derivatives with 2-bromomethyl-3,5,6-trimethylpyrazine. Another analogue of monastrol was accomplished by the reaction of 2-thioxopyrimidine derivatives with chloroacetamide, which was then reacted with 2-bromomethyl-3,5,6-trimethylpyrazine to afford ligustrazine-containing monastrol derivatives. The antiproliferative activity was assessed for all monastrol derivatives including ligustrazine nucleus against three major types of human tumor cell lines, including breast MCF-7, colon HCT-116, and liver HepG-2 cancer cell lines. Studies on molecular docking were directed to the most potent cytotoxic compounds within the active site of kinesin Eg5 protein.

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Funding

The researchers extend their appreciation to the National Research Center (Dokki, Cairo, Egypt) for funding the work through the research group project no. 12010106.

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Authors and Affiliations

  1. Applied Organic Chemistry Department, National Research Centre, 12622, Cairo, Egypt

    A. M. Mohamed, D. H. Elnaggar, M. A. Elsayed, N. A. Abdel-Hafez, M. E. A. Elasasy & A. E. Amr

  2. Organometallic and Organometalloid Chemistry Department, National Research Centre, 12622, Cairo, Egypt

    E. A. Mostafa

  3. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut Uniνersity, 71526, Assiut, Egypt

    B. G. M. Youssif

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  1. A. M. Mohamed
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  2. D. H. Elnaggar
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Correspondence to A. M. Mohamed.

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Mohamed, A.M., Elnaggar, D.H., Elsayed, M.A. et al. Design, Docking Studies, and Anticancer Activity of Newly Synthesized Monastrol Analogues Bearing Ligustrazine Moiety. Russ J Gen Chem 92, 2400–2414 (2022). https://doi.org/10.1134/S1070363222110251

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