Novel Schiff�s Base Containing Murrayanine- 1,3,4-Thiadiazole Hybrids as Potential Anti-Inflammatory Agents

Abstract

Murrayanine is the most highly explored molecule from Murraya koenigii L., known popularly as Indian curry plant (family Rutaceae) which demonstrates carminative, astringent, stomachic, purgative, febrifuge, anti-anemic, and anthelminthic. Thiadiazole is a scaffold of prime importance in medicinal chemistry. It has often been observed that thiadiazoles on hybridization with other heterocyclic scaffolds, demonstrates synergistic activity. Based on this fact, a hybrid of 1,3,4-thiadiazole was planned to fabricate with murrayanine and also to explore its synergistic potentials in a specific direction based on the available text information. The present study involved the synthesis of murrayanine-thiadiazole hybrids using a previously reported starting material (E)-2-((1-methoxy-9H-carbazol-3-yl)methylene)thiosemicarbazide and exploring the anti-inflammatory activity of the produced novel compounds. The compound 4c, containing 3-OCH 3 and 4-OH substituents displayed the highest edema reducing activity after 3 hrs. The enhanced activity may be due to the interaction of the hydrophilic moiety, via oxygen moiety with the active site of the inflammation causing elements like Cyclooxygenase (COX) and Lipoxygenase (LOX). We tried to establish a crystal clear structure-activity relationship, but due to mixed results, a true relationship cannot be predicted. Rather, an assumption was made based on the available interacting groups with the active sites of the chemical mediator. This research will definitely motivate global researchers in rationally designing of natural product-based heterocyclic hybrids which will have great perspective as therapeutic agents in future with reduced side-effects.

A Review on Synthesis, Therapeutic, and Computational Studies of Substituted 1, 3, 4 Thiadiazole Derivatives

“…Based on this fact, a hybrid of 1,3,4-thiadiazole was planned to fabricate with murrayanine and also to explore its synergistic potentials in a specific direction based on the available text information. Mahapatra et al 49 studied the synthesis of murrayanine-thiadiazole hybrids 62a-e (Scheme 33) using a previously reported starting material (E)-2-((1-methoxy-9Hcarbazol-3-yl)methylene)thiosemicarbazide and exploring the anti-inflammatory activity of the produced novel compounds. The compound 62c, containing 3-OCH 3 and 4-OH substituents displayed the highest edema reducing activity after 3 hrs.…”

“…Rather, an assumption was made based on the available interacting groups with the active sites of the chemical mediator. 49 Three new series of (E)-3-(4-substitutedphenyl)-N-(5phenyl-1,3,4-thiadiazol-2-yl)acrylamide derivatives (63a-f), 4-(4-substitutedphenyl)-N-(5-phenyl-1,3,4thiadiazol-2-yl)-1H-pyrazole-3-carboxamide derivatives (64a-f) and 4-(4-substitutedphenyl)-N-(5-phenyl-1,3,4-thiadiazol-2-yl)-1H-pyrrole-3carboxamide derivatives (65a-f) (Scheme 34) were synthesized and characterized by elemental analysis LCMS mass, FT-IR spectra 1 H and 13 C NMR. All the synthesized compounds were screened for their antiinflammatory activity.…”

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

“…The lack of achieving these interactions leads to reduced pharmacological activity because it will unable to interact and fit with the active site of the receptor and cannot trigger the action. 25 On comparison of the activity with the previously synthesized heterocyclic analogs of murrayanine-chalcone (pyrimidine 13 , oxadiazole 6 , thiadiazole 8 , and methylenedioxy 16 ), it was noticed that the activity of the hydroxylated compounds was low. This study provided some clues for better optimization of the structure to achieve the pronounced biological activity ( Table 1).…”

“…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, anticonvulsant, 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.…”

Piperidine containing Murrayanine-Chalcones as Emerging Bactericidal and Fungicidal Agents

“…Among the 20 other alkaloid molecules, murrayanine is the highest explored alkaloidal component present in the curry plant. Very recently, we have explored the pharmacological perspectives of the semi-synthetic products of this molecule and rationally developed the heterocyclic hybrids of murrayanine page no: 88 such as benzodiazepine [8] , benzothiazepine [9] , benzoxazepine [10] , chalcone [11][12][13][14] , hydantoin [15] , imidazole [16] , isoxazole [17] , oxadiazole [18] , phthalimide [19] , pyrazole [20] , pyrimidine [21] , Schiff's base analog [22] , thiadiazole [23] , thiazole [24] , and uracil [25][26][27] , and explored multifarious pharmacological activities such as anxiolytic, anti-cancer, anti-convulsant, anti-inflammatory, anti-microbial, anti-oxidant, etc. Likewise, in the current research, a piperidine containing chalcone was rationally developed by incorporating the natural portion (murrayanine) in the A-ring and a synthetic component (piperidine containing acetophenone) in the B-ring and screened against bacterial and fungal species.…”