Med Chem Res
NMR (CDCl3, 400 MHz) d (ppm) = 6.83 (1H, s),
6.90–6.93 (1H, dd, J = 2.20, 8.72 Hz), 6.98 (1H, d,
J = 2.16 Hz) 7.33 (1H, m), 7.54–7.59 (2H, m), 7.75–7.79
(1H, dt, J = 3.96, 7.92 Hz), 7.83 (1H, d, J = 7.88 Hz),
7.92 (1H, d, J = 8.72 Hz); 13C NMR (100 MHz,
d6-DMSO) d = 176.5, 163.6, 162.8, 160.4, 157.4, 133.6,
130.6, 126.2, 121.7, 117.9, 116.1, 114.9, 112.8, 107.2,
102.3. MS [ESI (?), m/e]: 241.08 (M ? H, 100 %).
(1H, s, ArH), 6.58 (1H, s, ArH); 13C NMR (100 MHz,
d6-DMSO) d = 181.9, 162.9, 153.1, 150.0, 146.6, 131.1,
131.0, 128.9, 128.6, 125.7, 104.3, 104.2, 93.8. MS [ESI
(?), m/e]: 271 [M? ?1].
2-(20,40-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-
one (5e) Light Brown amorphous powder The synthesis
was performed according to the general procedure given in
section 8.1, 2,4,6-trihydroxyacetophenone (1, 1.80 g,
4.3 mol) was stirred in the solution of sodium hydroxide in
water (40 mL) and 95 per cent alcohol (20 mL) with sub-
sequently addition of benzaldehyde (2, 1.48 g, 4.3 mol). The
resulted precipitates of 20-hydroxychalcone (3j, 0.006 mol)
were dissolved in a mixture of pyridine (10 mL) and aqueous
KOH (10 %, 24 mL) and were warmed to 60–70 °C in a
water bath. By the addition of hydrogen peroxide (10 %,
12 mL) with stirring gave the insoluble fraction, which was
separated by extraction with ether. The alkaline solution on
2-(30-Chlorophenyl)-4H-chromen-4-one (5b) Light yel-
lowish brown, amorphous powder The synthesis was per-
formed according to the general procedure given in
section 8.1, o-hydroxyacetophenone (1.2 mL, 0.1 mol) and
3-chlorobenzoyl chloride (2.62 g, 0.15 mol) were stirred in
2 mL of dry pyridine to afford the compound 5b. 83 %; mp
°
221–227 C; FTIR (neat) mmax: 1633 cm-1 (s), (C–Cl)
1092 cm-1 (w), (C–O) 1363–1006 cm-1
;
1H NMR
(CDCl3, 400 MHz) d (ppm) = 8.23 (1H, dd, J = 1.56,
7.96 Hz, ArH), 7.94 (1H, t, J = 1.4 Hz, ArH), 7.81 (1H, dt,
J = 1.36, 7.68 Hz, ArH), 7.71–7.75 (1H, m, ArH), 7.59
(1H, d, J = 8.04 Hz, ArH), 7.42–7.53 (3H, m, ArH), 6.82
(1H, s, ArH); 13C NMR (100 MHz, d6-DMSO) d = 178.1,
160.6, 156.2, 148.8, 134.4, 133.7, 131.8, 130.3, 126.0,
125.9, 125.8, 124.0, 121.3, 118.2, 108.9. MS [ESI (?),
m/e]: 257.00 (M ? H, 100 %).
acidification with hydrochloric acid gave substituted 3-hy-
°
droxyflavone (5e). 64 %; mp 301–307 C; FTIR (neat) mmax
:
(C = C) 1614 cm-1 (s), (C=O) 1661 cm-1 (s), (O–H)
3375 cm-1 (w); 1H NMR (DMSO-d6, 400 MHz) d
(ppm) = 12.48 (1H, s, ArOH), 10.45 (1H, s, ArOH), 9.63
(2H, s, ArOH), 8.05 (1H, s, ArOH), 7.25 (1H, d,
J = 8.44 Hz, ArH), 6.39 (1H, d, J = 2.2 Hz, ArH), 6.36
(1H, dd, J = 8.48, 2.2 Hz, ArH), 6.25 (1H, d, J = 2.04 Hz,
ArH), 6.12 (1H, d, J = 2.08 Hz, ArH); 13C NMR (100 MHz,
d6-DMSO) d = 175.9, 163.5, 160.9, 160.5, 156.8, 156.4,
148.4, 135.6, 131.1, 109.3, 107.1, 103.5, 103.1, 97.9, 93.2.
MS [ESI (?), m/e]: 303 [M? ?1].
2-(30-Nitrophenyl)-4H-chromen-4-one (5c) Light yellow,
crystalline solid The synthesis was performed according to
the general procedure given above, o-hydroxyacetophe-
none (1.2 mL, 0.1 mol) and 4-nitrobenzoyl chloride (2.7 g,
0.15 mol) were stirred in 2 mL of dry pyridine afford
°
compound 5c. 90 %; mp 251–256 C; FTIR (neat) mmax
:
(C=O) 1631.49 cm-1 (m), (N=O) 1516, 1372 cm-1 (w),
Biological evaluation
1
(C–O) 1363–1006 cm-1; H NMR (CDCl3, 400 MHz) d
(ppm) = 8.83 (t, 1H, J = 1.84 Hz, ArH), 8.40 (2H, dd,
J = 0.92, 2.28 Hz, ArH), 8.24–8.27 (1H, m, ArH),
7.74–7.78 (2H, m, ArH), 7.65 (1H, d, J = 7.76 Hz, ArH),
7.46–7.50 (1H, m, ArH), 6.92 (1H, s, ArH); 13C NMR
(100 MHz, d6-DMSO) d = 178.3, 161.8, 156.2, 135.3,
134.0, 133.6, 131.5, 130.4, 126.4, 125.8, 125.5, 124.4,
123.9, 118.1, 108.2. MS [ESI (?), m/e]: 268.07 (M ? H,
100 %).
Aldose reductase inhibitory activity
In order to perform ALR2 inhibitory activity assay, fol-
lowing chemicals and materials were procured and used for
study. DL-glyceraldehyde (Sigma Aldrich), NADPH and
2-mercaptoethanol (Himedia Laboratories Pvt. Ltd.,
Mumbai), epalrestat (Microlabs Ltd.), sodium carbonate,
dipotassium hydrogen orthophosphate, ammonium sulfate,
lithium sulfate and sodium hydroxide (Loba Chemicals
Pvt. Ltd., Mumbai). All required solutions for study were
freshly prepared, and goat eyes were obtained from a local
abattoir soon after slaughtering.
5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one (5d) Yel-
lowish crystalline solid The synthesis was performed
according to the general procedure using given in sec-
tion 8.1,
2,4,5,6-tetrahydroxyacetophenone
(1.84 g,
0.1 mol) and benzoyl chloride (2.10 mL, 0.15 mol) were
stirred in 2 mL of dry pyridine to afford compound 5d.
68 %; mp 254–258 °C; FTIR (neat) mmax: (C = C)
1611 cm-1 (m), (C=O) 1652 cm-1 (s), (O–H) 3398 cm-1
(w); 1H NMR (DMSO-d6, 400 MHz) d (ppm) = 10.11
(1H, s, ArOH), 8.59 (1H, s, ArOH), 7.93–7.95 (2H, m,
ArH), 7.90 (1H, s, ArOH), 7.51–7.55 (3H, m, ArH), 6.68
The eye lenses of a freshly slaughtered goat were surgi-
cally removed, washed with cold distilled water and
homogenized in cold water (distilled) containing 10 mM
2-mercaptoethanol (1:3 w/v). The homogenate was cen-
°
trifuged (10,000 rpm) for 30 min at 4 C, and thereafter, the
supernatant liquid was saturated by adding 40 % ammonium
sulfate. The saturated solution was filtered, and the filtrate
123