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Letters in Drug Design & Discovery

Author(s): Rania B. Bakr* and Nadia A.A. Elkanzi

DOI: 10.2174/1570180819666220106112650

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Novel 1,2-Thiazine-Pyridine Hybrid: Design, Synthesis, Antioxidant Activity and Molecular Docking Study

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Abstract

Objectives: 1,2-thiazine and pyridine heterocycles drew much attention due to their biological activities, including antioxidant activity. Based on fragment-based drug design, novel pyrido[1,2]thiazines 9a-c, thiazolidinopyrido[1,2], thiazines 10a-c and azetidinopyrido[1,2]thiazines 11a-c were designed and prepared.

Methods: These novel derivatives 9a-c, 10a-c and 11a-c were subjected to screening for their antioxidant activity via various assays as DPPH radical scavenging potential, reducing power assay and metal chelating potential.

Results: All the assayed derivatives exhibited excellent antioxidant potential and the tested compounds 9a, 9b, 10a, 10b, 11a and 11b exhibited higher DPPH scavenging potential (EC50 = 32.7, 53, 36.1, 60, 40.6 and 67 μM, respectively) than ascorbic acid (EC50 = 86.58 μM). While targets 9a, 10a and 11a (RP50 = 52.19, 59.16 and 52.25 μM, respectively) exhibited better reducing power than the ascorbic acid (RP50 = 84.66 μM). The computational analysis had been utilized to prophesy the bioactivity and molecular properties of the target compounds.

Conclusion: To predict the binding manner of the novel derivatives as antioxidants, in-silico docking study was performed on all the newly prepared compounds inside superoxide dismutase (SOD) and catalase (CAT) active site. The most active antioxidant candidate 9a (EC50 = 32.7 μM, RP50 = 52.19 μM) displayed excellent binding with Lys134 amino acid residing at Cu-Zn loop of SOD with binding energy score = -7.54 Kcal/mol, thereby increasing SOD activity and decreasing reactive oxygen species.

Keywords: 2, 2-diphenyl-1-picrylhydrazyl, reducing power, reactive oxygen species, antioxidant, docking study, synthesis.

Graphical Abstract

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