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Synthesis and Biological Activities of Some 3,5-Disubstituted-6-Oxo-1,2,4-Triazine-2-Thiocarboxamide Derivatives as Anti-Breast Cancer (MCF) and α-Glucosidase Inhibitors

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Abstract

A new series of trisubstituted-1,2,4-triazin-6-one derivatives (III–VIII) containing cinnmylidene and disubstituted phenyl (bearing acetoxy and methoxy) moieties have been synthesized, using 1,3-oxazolinone derivatives (IIa,b) and thiosemicarbazide as the key starting materials. The structures of the new 1,2,4-triazine-6-ones were confirmed by spectral data along with elemental microanalyses. The tittle compounds were screened for their cytotoxicity against breast cancer cell lines (MCF-7) as well as normal breast HDF. The tested 1,2,4-triazine-6-one derivatives revealed good cytotoxicity and selectivity towards breast cancer cell lines (MCF-7) relative to normal cells. Also, the compounds were tested for their potential to inhibit the activity of enzyme α-glucosidase. Meanwhile, most of the compounds exhibit the strongest enzyme inhibitory activity, while three compounds 5-cinnamylidene-3-(3,4-dimethoxy) phenyl-6(1H)-oxo-1,2,4-triazin-2-thiocarboxamide (IIIb), N-(4-chlorobenzoyl) methyl-5-cinnamylidene-6H-oxo-3-(3,4-dimethoxy) phenyl-1,2,4-triazin-3-thiocarboxamide (VI) and 5-cinnamylidene-3-(3,4-dimethoxy) phenyl-1,2,4-triazin-6-one (VIII) exhibited excellent activity with IC50 values 0.20, 0.33 and 0.080 mg/mL for α-glucosidase compared to1.22 mg/mL of Acarbose is used as a standard.

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Funding

Princess Nourah bint Abdulrahman University Researchers Supporting Project no. PNURSP2023R76, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

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Authors and Affiliations

  1. Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, 11671, P.O. Box 84428, Riyadh, Saudi Arabia

    Ghaferah H. Al-Hazmi

  2. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Suez Canal University, 41522, Ismailia, Egypt

    Manar G. Salem

Authors
  1. Ghaferah H. Al-Hazmi
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Correspondence to Ghaferah H. Al-Hazmi.

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Ghaferah H. Al-Hazmi, Manar G. Salem Synthesis and Biological Activities of Some 3,5-Disubstituted-6-Oxo-1,2,4-Triazine-2-Thiocarboxamide Derivatives as Anti-Breast Cancer (MCF) and α-Glucosidase Inhibitors. Russ J Bioorg Chem 49, 867–881 (2023). https://doi.org/10.1134/S1068162023040039

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