Water Mediated One-Pot, Stepwise Green Synthesis, Anti-Inflammatory
and Analgesic Activities of (3-Amino-1-Phenyl-1H-Benzo[f]Chromen-2-yl)
(1H-Indol-3-yl) Methanone Catalysed by L-Proline
Authors: Reddy G. Ganga , Reddy Ch. Venkata Ramana , Reddy B. Srinivasa 
Published: December 2021

Aim:

The reactions were carried out by one pot three-component synthesis, 3-
cyanoacetylindole (1) on reaction with aromatic aldehydes (2) and β-naphthol (3) in an aqueous
medium in the presence of L-proline as a catalyst under reflux for 30 min, resulting in (3-amino-1-
phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-yl)methanone (4). The method has many advantages
like short reaction times, good yields, and simple workup procedure, besides being green in nature.
Pharmacological evaluation of title compounds was done for anti-inflammatory and analgesic activities.
Anti-inflammatory activity was carried carrageenan-induced paw edema model in which indomethacin
was used as standard and analgesic activity was evaluated by eddy's hot plate method using
diclofenac as standard drug.

Background:

Benzopyrans or chromenes are an important class of heterocyclic compounds due to
their broad spectrum of biological activity and a wide range of applications in medicinal chemistry.
The chromene moiety is found in various natural products with interesting biological properties.
Chromenes constitute the basic backbone of various types of polyphenols and are widely found in
alkaloids, tocopherols, flavonoids, and anthocyanins. Indoles are omnipresent in various bioactive
compounds like alkaloids, agrochemicals, and pharmaceuticals.

Objective:

The objective of this study is to synthesize one-pot stepwise Green synthesis, antiinflammatory
and analgesic activities of 3-amino-1-phenyl-1H-benzo[f]chromen-2-yl) (1H-indol-3-
yl) methanones.

Methods:

The acute anti-inflammatory effect was evaluated by carrageenan-induced mice paw edema
(Ma Rachchh et al., 2011). Edema was induced by injecting carrageenan (1% w/v, 0.1 ml) in the
right hind paw of mice. The test compounds 1-12, indomethacin (10 mg/kg), and the vehicle were
administered orally one hour before injection of carrageenan. Paw volume was measured with a digital
plethysmometer at 0, 30, 60, 90, 120 min after injection. Percentage increase =A-B/ A *100

Results:

Carrageenan induced paw edema model was used for anti-inflammatory activity in which
animals treated with standard (indomethacin) and test compounds showed a significant decrease in
the paw edema. Analgesic activity was estimated using Eddy’s hot plate method; animals were treated
with standard (diclofenac) and test compounds showed a significant increase in the reaction time.

Conclusion:

A green, one-pot, step-wise and three-component synthesis of 3-amino-1-phenyl-1Hbenzo[
f]chromen-2-yl) (1H-indol-3-yl) methanone was achieved by using water as a solvent, Lproline
as catalyst under reflux conditions. The reactions were carried out in eco-friendly conditions
with shorter reaction times, easier workup, and high yields. Anti-inflammatory activity was evaluated
by carrageenan-induced paw edema model, where significant anti-inflammatory activity is shown by
all the test compounds 4(a-l) compared to standard drug. Analgesic activity was studied by Eddy’s
Hot plate method and Test compounds 4e, 4f, 4h, 4i, 4j, 4k, 4l showed significant activities compared
to the reference drug.