Nostotrebin 6, a bis(cyclopentenedione) with cholinesterase inhibitory activity isolated from Nostoc sp. str. Lukešová 27/97

Figures & data

Figure 1.  Chemical structure diagram of nostotrebin 6, shown together with the fragmentation scheme of the collision-induced dissociation of the molecular ion [M + H]⁺ of nostotrebin 6.

Figure 2.  Molecular structure of nostotrebin 6 with the C–H…O intramolecular hydrogen bonds shown (dashed lines). The stacking interactions between phenolic fragments are also shown.

Figure 3.  Lineweaver–Burk plot of AChE activity in the absence (▪) and in the presence of nostotrebin 6 at different concentrations: 2.25 μM (□), 3.38 μM (•), 4.50 μM (○), 5.64 μM (▴), 6.76 μM (▵), 9.00 μM (♦), and 11.00 μM (◊).

Figure 4.  Analysis of the multiple inhibition of AChE by nostotrebin 6. (A) Replots constructed from data of the Lineweaver–Burk plot, as described in Figure 3: (•) K_{m app}/V_app vs. [nostotrebin 6], (○) 1/V_app vs. [nostotrebin 6]. (B) Dependence of 1/K_{i slope} vs. [nostotrebin 6]. (C) Hill plot for AChE inhibition by nostotrebin 6 in the presence of 1.25 mM ATCI. (D) Dependence of v vs. [nostotrebin 6] for the hydrolysis of 1.25 mM ATCI by AChE.

Table 1.  Cholinesterase inhibitory effects of nostotrebin 6, galanthamine, and tacrine in vitro.

Inhibitor	IC50 (μM)		Selectivity BChE/AChE
	AChE	BChE
Nostotrebin 6	5.5	6.1–7.5^b	1.4
Galanthamine	0.3–0.5^a	8.6–37.9^b	70.2
Tacrine	0.057	0.0062–0.012^b	0.2

^aFor ATCI substrate range of 0.062–1.25 mM.

^bFor BTCI substrate range of 0.16–2.27 mM.

Figure 5.  Lineweaver–Burk plot of BChE activity in the absence (▪) and in the presence of nostotrebin 6 at different concentrations: 2.25 μM (□), 3.38 μM (•), 4.50 μM (○), 5.64 μM (▴), 6.76 μM (▵), 9.00 μM (♦), and 11.00 μM (◊).

Figure 6.  Analysis of the multiple inhibition of BChE by nostotrebin 6. (A) Replots constructed from data of the Lineweaver–Burk plot, as described in Figure 5: (•) K_{m app}/V_app vs. [nostotrebin 6], (○) 1/V_app vs. [nostotrebin 6]. (B) Dependence of 1/K_{i slope} vs. [nostotrebin 6]. (C) Hill plot for BChE inhibition by nostotrebin 6 in the presence of 0.908 mM BTCI. (D) Dependence of v vs. [nostotrebin 6] for the hydrolysis of 0.908 mM BTCI by BChE.