Rational Design, Synthesis, In Vitro, and In Silico Studies of Dihydropyrimidinone Derivatives as β-Glucuronidase Inhibitors

Table 2

Docking energies and interactions of compounds against the β-glucuronidase enzyme.

Compound	ΔG (kcal/Mol)	Category (type)	Ligand involved moiety	Receptor involved part	Distance (Å)
4a	−6.0	Hydrophobic (pi-pi stacked)	Phenyl ring	Tyr508	4.39
4b	−6.7	Hydrogen bond	O (C=O pyrimidinone ring)	Lys606	2.33
		Hydrogen bond	H (N-H pyrimidinone ring)	Glu540	2.74
		Hydrogen bond	H (N-H pyrimidinone ring)	Asp207	2.07
		Hydrophobic (pi-sigma)	C-H (Et)	Tyr508	3.78
4c	−7.1	Hydrogen bond	O (NO2)	His385	2.105
		Hydrogen bond	O (NO2)	Asn450	1.85
		Hydrogen bond	C-H (Et)	Asp207	3.43
4d	−7.1	Hydrogen bond	O (NO2)	Asp207	1.98
		Hydrogen bond	O (NO2)	His385	2.21
		Hydrogen bond	O (NO2)	Asn450	2.26
		Hydrogen bond	O (C=O amide)	Asn484	2.38
4e	−6.7	Hydrogen bond	O (C=O pyrimidinone ring)	Trp507	2.75
		Hydrophobic (pi-pi stacked)	Phenyl ring	Trp507	4.25
		Hydrophobic (pi-pi stacked)	Phenyl ring	Trp507	3.69
		Hydrophobic (pi-alkyl)	Cl	Trp507	4.27
		Hydrophobic (pi-alkyl)	Cl	Tyr561	4.23
4f	−6.1	Hydrophobic (pi-sigma)	C-H (Et)	Trp587	3.87
		Hydrophobic (pi-pi stacked)	Phenyl ring	Tyr508	4.53
4g	−6.6	Hydrogen bond	C-H (Et)	Tyr508	3.24
		Hydrophobic (pi-sigma)	C-H (Et)	Trp587	3.88
		Hydrophobic (pi-pi stacked)	Phenyl ring	Tyr508	4.37
4h	−7.0	Hydrogen bond	OH	His385	2.82
		Hydrogen bond	O (C=O pyrimidinone ring)	Asn484	2.15
		Hydrogen bond	O (C=O amide)	Tyr508	2.43
		Hydrogen bond	H (pyrimidinone ring)	Tyr508	3.25
		Hydrogen bond	C-H (Et)	Asp207	3.39
		Hydrophobic (pi-pi T-shaped)	Phenyl ring	Trp587	5.38
4i	−7.2	Hydrogen bond	O (C=O amide)	Asn484	2.95
		Hydrogen bond	O (C=O pyrimidinone ring)	Lys606	2.55
		Hydrogen bond	H (N-H pyrimidinone ring)	Asp207	2.25
		Hydrogen bond	H (N-H pyrimidinone ring)	Tyr504	3.36
		Hydrophobic (pi-sigma)	Thiophene ring	Asp207	3.72
		Hydrophobic (pi-sigma)	C-H (Et)	Typ508	3.66