Naphthoquinones from Diospyros lotus as potential urease inhibitors: In vitro and in silico studies.

• Three naphthoquinones di-naphthodiospyrol (A-C) were isolated from Diospyros lotus. • Di-naphthodiospyrol A (1) exhibited 94.2 % urease inhibition activity at 2 µM. • Di-naphthodiospyrol B and C also showed 87.4 and 88.4 % urease inhibition activity at 2 µM. • Diospyros lotus can be utilized for cure of ulcer. Urease is a metallo-protein in which two nickel (Ni) atoms are present at the active site. It is found in all the organisms such as, bacteria, fungi, plants, and in algae. Urease enzymes are also involved in catalyzing the hydrolysis of urea into CO 2 and NH 3. Urease is a virulence factor found in various pathogenic bacteria. It is essential in colonization of a host organism and in maintenance of bacterial cells in tissues. Due to its enzymatic activity, urease has a toxic effect on human cells. Current research work aimed to purify the three di-naphthodiospyrols namely; 5,4 -dihydroxy-1-methoxy-6,6 -dimethyl7,3-binaphthyl-1,4,5,8-tetraone (1), 5,8 -dihydroxy-5-methoxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4 -tetraone (2) and 8,5,8-trihydroxy-6,6-dimethyl-7,3-binaphthyl-1,4,1,4-tetraone (3) from the chloroform fraction of Diospyros lotus roots. The pure constituents (1-3) were evaluated for their urease inhibitory activity. Compounds (1-3) exhibited potent activity with IC 50 value of 28.27 ± 1.68, 20.57 ± 2.00, 27.12 ± 2.45 µ M respectively, when compared with standard thiourea (IC 50 = 21.23 ± 0.12 µ M). The pure isolated compounds (1-3) were also subjected to in silico studies to know their binding pattern with enzyme. The binding orientation and interactions with the important residues of urease enzyme revealed that the three compounds inactivate the enzyme activity by interacting with Ni bi-center as well as with the tailpiece residues. [ABSTRACT FROM AUTHOR]