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

Abstract

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.

Keywords: L-proline; Water; analgesic activity; anti-inflammatory; green conditions; multi-component reaction; one-pot.