New 2-Oxopyridine/2-Thiopyridine Derivatives Tethered to a Benzotriazole with Cytotoxicity on MCF7 Cell Lines and with Antiviral Activities

Author(s): Adel Mahmoud Attia, Ahmed Ibrahin Khodair*, Eman Abdelnasser Gendy, Mohammed Abu El-Magd, Yaseen Ali Mosa Mohamed Elshaier*

Journal Name: Letters in Drug Design & Discovery

Volume 17 , Issue 2 , 2020


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Abstract:

Background: Perturbation of nucleic acids structures and confirmation by small molecules through intercalation binding is an intriguing application in anticancer therapy. The planar aromatic moiety of anticancer agents was inserted between DNA base pairs leading to change in the DNA structure and subsequent functional arrest.

Objective: The final scaffold of the target compounds was annulated and linked to a benzotriazole ring. These new pharmacophoric features were examined as antiviral and anticancer agents against MCF7 and their effect on DNA damage was also assessed.

Methods: A new series of fully substituted 2-oxopyridine/2-thioxopyridine derivatives tethered to a benzotriazole moiety (4a-h) was synthesized through Michael cyclization of synthesized α,β- unsaturated compounds (3a-e) with appropriate active methylene derivatives. The DNA damage study was assessed by comet assay. In silico DNA molecular docking was performed using Open Eye software to corroborate the experimental results and to understand molecule interaction at the atomic level.

Results: The highest DNA damage was observed in Doxorubicin, followed by 4h, then, 4b, 4g, 4f, 4e, and 4d. The docking study showed that compound 4h formed Hydrogen Bonds (HBs) as a standard ligand with GSK-3. Compound 4h was the most active compound against rotavirus Wa, HAVHM175, and HSV strains with a reduction of 30%, 40%, and 70%, respectively.

Conclusion: Compound 4h was the most active compound and could act as a prospective lead molecule for anticancer agent.

Keywords: Pyridin-2-ones, pyridin-2-thiones, benzotriazole, antitumor-antiviral, DNA-docking, open eye software.

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VOLUME: 17
ISSUE: 2
Year: 2020
Published on: 13 February, 2020
Page: [124 - 137]
Pages: 14
DOI: 10.2174/1570180816666190220123547
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