Synthesis and studies molecular docking of some new thioxobenzo[g]pteridine derivatives and 1,4-dihydroquinoxaline derivatives with glycosidic moiety

Figures & data

Scheme 1. Synthesis of compounds 3 and 4.

Scheme 2. Synthesis of O-acetyl-β-D-glucopyranosyl-thioxobenzo[g]pteridin-derivatives 8 and 9.

Scheme 3. Synthesis of compounds 14, 15 and 16.

Table 1. Molecular modelling data for compounds 4, 8, 9, 16 and S-58 during docking in the active site of the COX-2 enzyme (PDB: ID 1CX2).

Compound No.	Affinity Kcal/mol	No.of hydrogen bonds	Distance (A^o) from main residue		Functional Group
4	−13.53	3	2.41	His90	Oxadiazole N
			2.21	Arg120	C = O
			2.87	Tyr355	C = O
8	−12.27	3	2.22	Leu352	NH
			2.65	Gln292	C = O
			2.85	Arg513	C = O
9	−12.62	3	2.33	Ser530	acetyl-C = O
			2.25	Arg513	Pteridine C = O
			2.11	Tyr355	Acetyl C = O
16	−11.50	3	3.15	His90	−C = O
			2.17	Arg513	−C = O
			2.07	Arg120	−C = O
S-58	−11.93	2	2.41	Arg513	−SO2
			2.30	His90	−SO2

Figure 1. A) Binding of the candidate 4 with COX-2 (using MOE site finder programme), the dotted lines represent H-bonding interactions between oxadiazole N and His90 and between the acetyl C = O atom and Tyr355& Arg120. B) 3D interactions of 4 with Tyr355, Arg120, and His90 acid residues.

Figure 2. A) Binding of the candidate 8 with COX-2 (using MOE site finder programme), the dotted lines represent H-bonding interactions between NH and Leu352, pteridine C = O, and Gln292 and between the acetyl C = O atom and Arg513. B) 3D interactions of 8 with Leu352, Gln292, and Arg513 acid residues.

Figure 3. A) Binding of the candidate 9 with COX-2 (using MOE site finder programme), the dotted lines represent H-bonding interactions between acetyl C = O and Ser530 & Tyr385 and pteridine C = O and Arg513 and the arene cation interactions between the phenyl ring and Arg513 & Arg120. B) 3D interactions of 9 with Ser530 & Tyr385 and Arg513 acid residues.

Figure 4. A) Binding of the candidate 16 with COX-2 (using MOE site finder programme), the dotted lines represent H-bonding interactions between acetyl C = O and His90 & Arg513 and Arg120 and the arene cation interactions between the benzene ring and Arg120. B) 3D interactions of 16 with His90 & Arg513 and Arg120 acid residues.