Synthesis, Molecular Docking and Pharmacological Study of Pyrimidothiadiazinones and its bis-derivatives

Title:Synthesis, Molecular Docking and Pharmacological Study of Pyrimidothiadiazinones and its bis-derivatives

Volume: 14 Issue: 4

Author(s): Sobhi M. Gomha, Ikhlass M. Abbas, Mohamed A. A. Elneairy, Mahmoud M. Elaasser and Bazada K. A. Mabrouk

Affiliation:

Keywords: Mannich reaction, 1, 3, 5-thiadiazines, molecular docking, antimicrobial and anticancer activities.

Abstract: Background: A series of pyrimidothiadiazinones 5a-n were prepared from aminomethylation of pyrimidinethione 1 with different primary amines and formaldehyde through Mannich reaction. The spectral data of the formed products confirmed the suggested structures.

Method: Most of the newly synthesized compounds were tested for their antimicrobial and anticancer activities. Depending on the obtained results, the newly synthesized compounds possess good to moderate activities. Compound 5e exhibited the highest antibacterial activity measured in 22.1, 18.6, 17.2 and 16.8 mm against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Pseudomonas aeruginosa, respectively. Compound 5e exhibited highest potency with MIC values of 125, 250, 250, and 500 μg/mL against E. coli, S. aureus, B. subtilis, and P. aureginosa, respectively.

Results: Compound 5j exhibited the highest inhibitory effect against breast carcinoma (MCF-7) and hepatocellular carcinoma (HepG2) cell lines. Also, molecular docking against E. Coli Enoyl Reductase; PDB ID (1LXC) and Human Dihydrofolate Reductase; PDB ID (1DLS) revealed high free binding energy and good binding mode. The structure activity relationship (SAR) of tested compounds was also studied.

Cite this article as:

Gomha M. Sobhi, Abbas M. Ikhlass, Elneairy A. A. Mohamed, Elaasser M. Mahmoud and Mabrouk K. A. Bazada, Synthesis, Molecular Docking and Pharmacological Study of Pyrimidothiadiazinones and its bis-derivatives, Letters in Drug Design & Discovery 2017; 14 (4) . https://dx.doi.org/10.2174/1570180813666160815125409

DOI https://dx.doi.org/10.2174/1570180813666160815125409	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X