Synthesis and biological evaluation of novel angular fused Pyrrolocoumarins

Figures & data

Table I.  Interaction % with DPPH (RA %); Competition % with DMSO for hydroxyl radical (HO√ %); % Superoxide radical scavenging activity (PMS %).

Comp.	RA % 0.1 mM 20 min	RA % 0.1 mM 60 min	RA % 0.2 mM 20 min	RA % 0.2 mM 60 min	HO√ (%) 0.01 mM	HO√ (%) 0.1 mM	PMS% 0.1 mM
7	21.4	20.5	33	44.2	97	94.4	no
9	12.2	3.6	4.3	20.5	96	no	84.4
14	29.5	46.6	61.8	69.6	95	88.5	no
NDGA	81	82.6	80	80	nt	nt	nt
Warfarin	9.2	10	24	23.2	nt	nt	no^a
Trolox	nt	nt	nt	nt	73.4	88.2	nt
Caffeic Acid	nt	nt	nt	nt	nt	nt	47

^a25% (at 1 mM); nt: not tested; no: not determined under the reported experimental conditions.

Scheme 1 Reagents and conditions: (i) DCM, 0(C (45 min) and the reflux (6 h).

Scheme 2 Reagents and conditions: (i) DCM, r.t. (4 days).

Table II.  Inhibition % LOX / IC₅₀ values of soybean lipoxygenase; Inhibition % of induced carrageenin rat paw edema (CPE %) at 0.01 mmol/Kg body weight; Theoretically calculated lipophilicity values. [35]

Compounds	LOX % 0.1 mM	LOX % IC50 (mM)	CPE %^a	Clog P^b
7	62.4(0.01 mM) 71 (0.1 mM)		67.8*	1.60
9		0.325 mM	73.4 **	1.60
14		0.35 mM	60.5 *	1.24
Warfarin	no	no	41 **
Caffeic acid		0.6 mM	nt
Indomethacin	nt		47 *

^astatistical studies were done with student's T-test, * p < 0.01, ** p < 0.05

^b Biobyte Corp [35]; no: no action under the reported experimental conditions; nt: not tested.

Table III.  PT and aPTT values (sec) induced by the tested compounds

Compounds	PT (s)	aPT (s)
7	24	105
9	21.5	86
14	24	102
Warfarin	>50
Coumarin	19	35
Control	19	60

Biobyte Corp., C-QSAR Database 201 West 4th Str., Suite 204, Claremont, CA, California 91711, USA.

 Google Scholar