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

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 anti-helminthic. 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-OCH₃ 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.