Synthesis, antimicrobial activity and molecular modeling study of substituted 5-aryl-pyrimido[5,4-c]quinoline-2,4-diones

Figures & data

Figure 1.  Left panel: 2D sketch of the binding mode of Clorobiocin into its binding site of DNA gyrase-B, showing three hydrogen bonds as green dotted lines (with residues Arg136, Asp73 and Asn46) and one Pi-cationic interaction with Arg76; right panel: Docking validation of Clorobiocin with DNA gyrase-B: crystal structure ligand (red) docked ligand (yellow); RMSD 0.41 Å.

Figure 2.  Synthesis of pyrimido[5,4-c]quinoline-2,4-dione derivatives 5a–k.

Table 1.  In vitro antimicrobial activity of pyrimido[5,4-c]quinoline-2,4-diones 5a–k.

Compd #	Inhibition Zone Diameter (mm)
	B. subtilis (Gm +ve)	Staph. Aureus (Gm +ve)	Strept. faecalis (Gm +ve)	E. coli (Gm –ve)	P. aeruginosa (Gm –ve)
Tetracycline	32	28	31	30	31
(5a)	–	–	11	11	11
(5b)	–	–	11	–	–
(5c)	–	–	–	–	–
(5d)	13	13	14	14	14
(5e)	16	16	15	15	16
(5f)	15	15	14	15	15
(5g)	–	–	–	11	–
(5h)	15	14	16	15	16
(5i)	–	13	13	13	11
(5j)	–	11	–	11	–
(5k)	13	14	13	14	14

Figure 3.  2D Ligand interaction of the 5-aryl-pyrimido[5,4-c]quinoline-2,4-diones with DNA gyrase-B; panel (1) compound 5c showing only pi-cationic interaction with Arg76; panel (2) compound 5e showing pi-cationic interaction with Arg76 and H-bond with Arg136; panel (3) compound 5f showing pi-cationic interaction with Arg76 and two H-bonds with Arg136 and Asn46.

Figure 4.  3D overlay of Clorobiocin (green), 5c (yellow), 5e (blue) and 5f (red) in DNA-gyrase active pocket.