European Journal of Medicinal Chemistry 44 (1) 2009, 432-436 Rare dipeptide and urea derivatives from roots of Moringa Oleifera as potential anti-inflammatory and antinociceptive agents Koneni V. Sashidhara* a , Jammikuntla N. Rosaiah a , Ethika Tyagi b , Rakesh Shukla b , Ram Raghubir b , and Siron M. Rajendran c a Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, India b Division of Pharmacology, Central Drug Research Institute, Lucknow 226001, India c Botany Department, Central Drug Research Institute, Lucknow 226001, India Abstract - In the course of our studies on the isolation of bioactive compounds from the roots of Moringa Oleifera, a traditional herb in southeast Asia ,rare aurantiamide acetate 4 and 1,3-dibenzyl Urea 5 has been isolated, and its structure determined by extensive 2D NMR. And also this is the first report of isolation from this genus. Isolated compound inhibited the production of TNF-α, IL-2, further compound 5 showed significant analgesic activities in dose dependant manner. These findings may help in understanding the mechanism of action of this traditional plant leading to control activated mast cells on inflammatory conditions like arthritis, for which the crude extract has been used. Keywords: Aurantiamide acetate, 1,3-dibenzyl Urea, analgesic activity, TNF α, IL 2, IL 6. . CDRI communication No. 7008 (Part of this work was presented as poster in CTDDR Symposium-2007). *Corresponding author E-mail: sashidhar123@gmail.com (K V Sashidhara) Fax: +91-0522-2623405. Tel: +91 0522 2612411-18, Ext. 4406. Introduction The design and development of new molecules potentially useful in the control of pain is a very important area today. Over the last few years, the amount of information from studies on pain transmission by transient receptor potential channel, Vanilloid subfamily member 1(TRPV1) binding ligands has dramatically increased, thus revealing novel targets for the advent of new pain therapies. Moreover, a gigantic step came with the identification of a protein called TRPV1, cloned in 1997, which is a ligand-gated nonselective cation channel vanilloid receptor with high Ca 2+ permeability [1]. TRPV1 is a molecular integrator of nociceptive stimuli expressed predominantly on unmyelinated pain sensing nerve fibers (C-fibers) and small Aδ fibers in the dorsal root, trigeminal, and nodose ganglia.TRPV1 is activated not only by Vanilloid ligands such as capsaicin 1, noxious heat (> 42 0 C) and protons (extra cellar PH<6) but also by endogenous mediators of inflammation such as cannabinoid anandamide and arachidonic metabolites [2, 3]. Capsazepine 2, which has been extensively characterized, was the first reported competitive VR1 antagonist. However its drawback is its modest potency and poor metabolic and pharmacokinetic properties [4]. Recently the structure activity relationships of 1,3-