10.1021/ol4002976 r 2013 American Chemical Society Published on Web 04/03/2013 ORGANIC LETTERS 2013 Vol. 15, No. 8 1862–1865 New Inhibitors of ROS Generation and T‑Cell Proliferation from Myrtus communis M. Iqbal Choudhary, †,‡,§ Noureen Khan, † Manzoor Ahmad, 3 Sammer Yousuf, † Hoong-Kun Fun, ^, ) Samreen Soomro, ‡ M. Asif, ‡ M. Ahmed Mesaik, ‡ and Farzana Shaheen* ,† H. E. J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi-75270, Pakistan, Department of Chemistry, Faculty of Science, King Saud University, Riyadh-11451, Saudi Arabia, School of Physics, Universiti Sains Malaysia, Penang, 11800 Malaysia, Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia, and Department of Chemistry, University of Malakand, Chakdara, Dir (L.), Pakistan afnan.iccs@gmail.com Received February 22, 2013 ABSTRACT Phytochemical investigation on Myrtus communis Linn. afforded myrtucommuacetalone (1) with an unprecedented carbon skeleton and a new phloroglucinol-type compound, myrtucommulone M (2), along with four known constituents 36. Their structures were established by extensive analyses of NMR and mass spectral data as well as by single-crystal X-ray diffraction studies. These constituents were evaluated for their ability to modulate the immune response, based on their effects on various components of immune system. Compounds 1 and 5 exhibited significant inhibitory effect against nitric oxide (NO • ) production. Compound 1 also exhibited significant antiproliferative activity (IC 50 < 0.5 μg/mL) against T-cell proliferation. Myricetin (3) exerted a significant inhibition (IC 50 = 1.6 μg/mL) on zymosan-stimulated whole blood phagocytes ROS production. Compounds 1 and 3 were active against PMA-stimulated ROS generation. Myrtus communis Linn., commonly referred to as “True Myrtle”, is an evergreen shrub widely spread over the Mediterranean region. It is an important medicinal herb of the family Myrtaceae. 1,2 Myrtle has been traditionally used in folk therapeutic practices as an anti-inflammatory, antibacterial, antioxidant, antihyperglycemic, and anal- gesic agent, as well as for the treatment of oral dis- eases, candidiasis, wounds, and urinary disorders. 36 The major constituents of the plant include monoterpenoids, triterpenoids, flavonoids, and phloroglucinol derivatives. Previously, we reported several phloroglucinol-type com- pounds as antibacterial and R-glucosidase inhibitors from † H. E. J. Research Institute of Chemistry, University of Karachi. ‡ Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi. § Department of Chemistry, Faculty of Science, King Saud University. 3 Department of Chemistry, University of Malakand. ^ School of Physics, University Sains Malaysia. ) Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University. (1) Sumbull, S.; Ahmad, M. A.; Asif, M.; Akhtar, M. Indian J. Nat. Prod. Resour. 2011, 2, 395–402. (2) Akin, M.; Aktumsek, A.; Nostro, A. African J. Biotechnol. 2010, 9, 531–535. (3) Rosa, A.; Melis, M. P.; Deiana, M.; Atzeri, A.; Appendino, G.; Corona, G.; Incani, A.; Loru, D.; Dess  i, M. A. Chem. Phys. Lipids 2008, 155, 16–23. (4) Kathleen, G.; J€ urgen, M.; Oliver, W.; Manfred, S.-Z.; Mona, A.-T. Planta Med. 2011, 77, 450–454. (5) Mimica-Dukic, N.; Bugarin, D.; Grbovic, S.; Mitic-Culafic, D.; Vukovic-Gacic, B.; Orcic, D.; Jovin, E.; Couladis, M. Molecules 2010, 15, 2759–2770. (6) Babaee, N.; Mansourian, A.; Momen-Heravi, F.; Moghadamnia, A.; Momen-Beitollahi, J. Clin. Oral Invest. 2010, 14, 65–70.