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Mini-Reviews in Medicinal Chemistry


ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

Research Article

Design, Synthesis, Molecular Docking Study and Anti-Hepatocellular Carcinoma Evaluation of New Bis-Triazolothiadiazines

Author(s): Sobhi M. Gomha, Zeinab A. Muhammad*, Elham Ezz El-Arab, Amira M. Elmetwally, Abdelaziz A. El-Sayed and Islam K. Matar

Volume 20, Issue 9, 2020

Page: [788 - 800] Pages: 13

DOI: 10.2174/1389557519666191015130037

Price: $65


Objective: The reaction of bis(4-amino-4H-1,2,4-triazole-3-thiol) with hydrazonoyl halides and α-halo-ketones gave a new series of bis-1,2,4-triazolo[3,4-b]thiadiazine derivatives.

Methods: The structure of the new products was established on the basis of their elemental and spectral data (mass, 1H NMR, 13C NMR and IR) and an alternate method.

Results: Several of the synthesized products were subjected to in vitro anticancer screening against human hepatocellular carcinoma (HepG-2) and the results showed that compounds 16, 14 and 12 have promising activities (IC50 value of 24.8±9.1, 28.3±0.5, and 31±2.9μM, respectively) compared with Harmine reference drug (IC50 value of 22.4±1.11 μM).

Conclusion: Moreover, molecular docking studies were performed to analyze the binding modes of the discovered hits into the active site of DYRK1A using iGEMDOCK.

Keywords: 1, 4-dihydropyridines, triazolo-thiadiazines, hydrazonoyl halides, molecular docking, antitumor activities, in vitro.

Graphical Abstract
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