Exploring the site‒specific influence of hydroxyl group in ring‒B of murrayanine‒chalcone on edema reducing potential

Murraya koenigii L. (family: Rutaceae), also known as Indian curry plant is having ethnopharmacological importance.1 The plant parts (root, leaf, and stem bark) are known to have several biological activities like anti‒helminthic, carminative, stomachic, febrifuge, astringent purgative, etc.2 These activities are a function of the phytoconstituents of carbazole scaffolds like euchrestine B, mahanine, O‒ methylmurrayamine A, bismurrayafoline, murrayanine, bismahanine, koenimbine, mahaninebine, isomahanine, O‒methylmahanine, bispyrayafoline, and mahaninebicine which in scientific studies over the years have represented potent anti‒ulcerogenic, anti‒ bacterial, anti‒oxidant, anti‒fungal, immunomodulation, etc.3 Murrayanine is the most imperative, most active, and highly explored phytoconstituent which have been studied by our research group over the years.4 A chalcone derivative, designated by us as “Murrayanine‒ Chalcone” was synthesized,5 and a number of heterocyclic derivatives (oxadiazole,6 thiazole,7 thiadiazole,8 hydantoin,9 benzodiazepine,10 pyrazole,11 benzoxazepine,12 pyrimidine,13 benzothiazepine,14 isoxazole,15 3,4‒methylenedioxy,16 and phthalimide,17 were fabricated in order to amplify the biological activities (anti‒diabetic, anti‒inflammatory, anti‒oxidant, anti‒anxiety, antibacterial, anti‒ convulsant, and anti‒fungal) by using the most common strategy ‘hybridization’. Chalcone or 1,3‒diphenyl‒2E‒propene‒1‒one comprises of a benzylideneacetophenone scaffold where the two aromatic nuclei joined by a three carbon α, β unsaturated carbonyl bridge.18 This scaffold is easy to synthesize and exhibit diverse options for substitution and their profound capability to exhibit diverse biological activities such as hypoglycemic, hypolipidemic, antihypertensive, anti‒platelet, anti‒arrhythmic, anti‒obesity, anti‒ infective, etc.19‒21 Chalcones have tremendous potential of exhibiting anti‒inflammatory activity and the development of a chalcone analog of murrayanine may have the perspectives of better anti‒inflammatory activity than the parent moiety itself.22 In the present research, hydroxylated derivatives of murrayanine‒chalcone were rationally designed and synthesized from murrayanine (1) and hydroxylated acetophenones (2a‒c) to obtain hydroxylated derivatives using the previously reported protocol and to explore the anti‒inflammatory potential using carrageenan‒induced paw edema method. In addition to it, the establishment of the possible structure‒activity‒relationship (SAR) was done, which will be beneficial for the medicinal chemists in further designing target modulators.