Current Anti-Inflammatory Therapies and the Potential of Secretory Phospholipase A2 Inhibitors in the Design of New Anti-Inflammatory Drugs: A Review of 2012 - 2018

Author(s): Thais A. Sales*, Silvana Marcussi, Teodorico C. Ramalho*

Journal Name: Current Medicinal Chemistry

Volume 27 , Issue 3 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


The inflammatory process is a natural self-defense response of the organism to damage agents and its action mechanism involves a series of complex reactions. However, in some cases, this process can become chronic, causing much harm to the body. Therefore, over the years, many anti-inflammatory drugs have been developed aiming to decrease the concentrations of inflammatory mediators in the organism, which is a way of controlling these abnormal chain reactions. The main target of conventional anti-inflammatory drugs is the cyclooxygenase (COX) enzyme, but its use implies several side effects. Thus, based on these limitations, many studies have been performed, aiming to create new drugs, with new action mechanisms. In this sense, the phospholipase A2 (PLA2) enzymes stand out. Among all the existing isoforms, secretory PLA2 is the major target for inhibitor development, since many studies have proven that this enzyme participates in various inflammatory conditions, such as cancer, Alzheimer and arthritis. Finally, for the purpose of developing anti-inflammatory drugs that are sPLA2 inhibitors, many molecules have been designed. Accordingly, this work presents an overview of inflammatory processes and mediators, the current available anti-inflammatory drugs, and it briefly covers the PLA2 enzymes, as well as the diverse structural array of the newest sPLA2 inhibitors as a possible target for the production of new anti-inflammatory drugs.

Keywords: Phospholipases A2, inflammation, drug design, enzymatic inhibitors, anti-inflammatory drugs, newest patents.

Karmarkar, D. Modulators of the acute inflammatory response: a dissertation.. 2013.
Joshi, V.; Umashankara, M.; Ramakrishnan, C.; Nanjaraj Urs, A.N.; Suvilesh, K.N.; Velmurugan, D.; Rangappa, K.S.; Vishwanath, B.S. Dimethyl ester of bilirubin exhibits anti-inflammatory activity through inhibition of secretory phospholipase A2, lipoxygenase and cyclooxygenase. Arch. Biochem. Biophys., 2016, 598, 28-39.
[] [PMID: 27060751]
Rafaniello, C.; Ferrajolo, C.; Sullo, M.G.; Sessa, M.; Sportiello, L.; Balzano, A.; Manguso, F.; Aiezza, M.L.; Rossi, F.; Scarpignato, C.; Capuano, A. Risk of gastrointestinal complications associated to NSAIDs, low-dose aspirin and their combinations: Results of a pharmacovigilance reporting system. Pharmacol. Res., 2016, 104, 108-114.
[] [PMID: 26739516]
Ahmadi, A.; Khalili, M.; Olama, Z.; Karami, S.; Nahri-Niknafs, B. Synthesis and study of analgesic and anti-inflammatory activities of amide derivatives of ibuprofen. Mini Rev. Med. Chem., 2017, 17(9), 799-804.
[] [PMID: 28029080]
Cronstein, B.N.; Weissmann, G. Targets for antiinflammatory drugs. Annu. Rev. Pharmacol. Toxicol., 1995, 35, 449-462.
[] [PMID: 7598502]
Yousefpour, A.; Amjad Iranagh, S.; Nademi, Y.; Modarress, H. Molecular dynamics simulation of nonsteroidal antiinflammatory drugs, naproxen and relafen, in a lipid bilayer membrane. Int. J. Quantum Chem., 2013, 113(15), 1919-1930.
Marnett, L.J. The COXIB experience: a look in the rearview mirror. Annu. Rev. Pharmacol. Toxicol., 2009, 49(1), 265-290.
[] [PMID: 18851701]
Ramalho, T.C.; Rocha, M.; da Cunha, E.F.F.; Freitas, M.P. The search for new COX-2 inhibitors: a review of 2002 - 2008 patents. Expert Opin. Ther. Pat., 2009, 19(9), 1193-1228.
[] [PMID: 19563267]
Cannon, C.P.; Cannon, P. J. Physiology. COX-2 inhibitors and cardiovascular risk. Science, 2012, 336(6087), 1386-1387.
[] [PMID: 22700906]
Reid, R.C. Inhibitors of secretory phospholipase A2 group IIA. Curr. Med. Chem., 2005, 12(25), 3011-3026.
[] [PMID: 16378502]
Quach, N.D.; Arnold, R.D.; Cummings, B.S. Secretory phospholipase A2 enzymes as pharmacological targets for treatment of disease. Biochem. Pharmacol., 2014, 90(4), 338-348.
[] [PMID: 24907600]
Medzhitov, R. Inflammation 2010: new adventures of an old flame. Cell, 2010, 140(6), 771-776.
[] [PMID: 20303867]
Allen, J.; Sun, Y.; Woods, J.A. Exercise and the regulation of inflammatory responses. Prog. Mol. Biol. Transl. Sci., 2015, 135, 337-354.
[] [PMID: 26477921]
Zweifach, B.W.; Grant, L.; McCluskey, R.T. The Inflammatory Process; Elsevier Science, 2014.
Medzhitov, R. Origin and physiological roles of inflammation. Nature, 2008, 454(7203), 428-435.
[] [PMID: 18650913]
Agarwal, S.; Reddy, G.V.; Reddanna, P. Eicosanoids in inflammation and cancer: the role of COX-2. Expert Rev. Clin. Immunol., 2009, 5(2), 145-165.
[] [PMID: 20477063]
Khanapure, S.P.; Garvey, D.S.; Janero, D.R.; Letts, L.G. Eicosanoids in inflammation: biosynthesis, pharmacology, and therapeutic frontiers. Curr. Top. Med. Chem., 2007, 7(3), 311-340.
[] [PMID: 17305573]
Berry, E.; Liu, Y.; Chen, L.; Guo, A.M. Eicosanoids: Emerging contributors in stem cell-mediated wound healing. Prostaglandins Other Lipid Mediat., 2017, 132, 17-24.
[] [PMID: 27825971]
Balietti, M.; Giuli, C.; Fattoretti, P.; Fabbietti, P.; Postacchini, D.; Conti, F. Cognitive stimulation modulates platelet total phospholipases A2 activity in subjects with mild cognitive impairment. J. Alzheimers Dis., 2016, 50(4), 957-962.
[] [PMID: 26836161]
Burke, J.E.; Dennis, E.A. Phospholipase A2 biochemistry. Cardiovasc. Drugs Ther., 2009, 23(1), 49-59.
[] [PMID: 18931897]
Ong, W-Y.; Farooqui, T.; Kokotos, G.; Farooqui, A.A. Synthetic and natural inhibitors of phospholipases A2: their importance for understanding and treatment of neurological disorders. ACS Chem. Neurosci., 2015, 6(6), 814-831.
[] [PMID: 25891385]
Ramamoorthy, S.; Cidlowski, J.A. Corticosteroids: Mechanisms of action in health and disease. Rheum. Dis. Clin. North Am., 2016, 42(1), 15-31 [vii..
[] [PMID: 26611548]
Riedemann, T.; Patchev, A.V.; Cho, K.; Almeida, O.F. Corticosteroids: Way upstream the protagonists and their roles. Mol. Brain, 2010, 3(2)
[] [PMID: 20180948]
Cata, J.P.; Guerra, C.E.; Chang, G.J.; Gottumukkala, V.; Joshi, G.P. Non-steroidal anti-inflammatory drugs in the oncological surgical population: beneficial or harmful? A systematic review of the literature. Br. J. Anaesth., 2017, 119(4), 750-764.
[] [PMID: 29121285]
He, B.S.; Wang, J.; Liu, J.; Hu, X.M. Eco-pharmacovigilance of non-steroidal anti-inflammatory drugs: Necessity and opportunities. Chemosphere, 2017, 181, 178-189.
[] [PMID: 28437743]
Boggara, M.B.; Mihailescu, M.; Krishnamoorti, R. Structural association of nonsteroidal anti-inflammatory drugs with lipid membranes. J. Am. Chem. Soc., 2012, 134(48), 19669-19676.
[] [PMID: 23134450]
Badri, W.; Miladi, K.; Nazari, Q.A.; Greige-Gerges, H.; Fessi, H.; Elaissari, A. Encapsulation of NSAIDs for inflammation management: Overview, progress, challenges and prospects. Int. J. Pharm., 2016, 515(1-2), 757-773.
[] [PMID: 27829170]
Anelli, M.G.; Scioscia, C.; Grattagliano, I.; Lapadula, G. Old and new antirheumatic drugs and the risk of hepatotoxicity. Ther. Drug Monit., 2012, 34(6), 622-628.
[] [PMID: 23128910]
Blanca-Lopez, N.; Perez-Alzate, D.; Canto, G.; Blanca, M. Practical approach to the treatment of NSAID hypersensitivity. Expert Rev. Clin. Immunol., 2017, 13(11), 1017-1027.
[] [PMID: 28893093]
Gaddipati, R.S.; Raikundalia, G.K.; Mathai, M.L. Dual and selective lipid inhibitors of cyclooxygenases and lipoxygenase: A molecular docking study. Med. Chem. Res., 2014, 23(7), 3389-3402.
Pyasi, K.; Tufvesson, E.; Moitra, S. Evaluating the role of leukotriene-modifying drugs in asthma management: Are their benefits ‘losing in translation’? Pulm. Pharmacol. Ther., 2016, 41, 52-59.
[] [PMID: 27651322]
Patrono, C. Cardiovascular effects of nonsteroidal anti-inflammatory drugs. Curr. Cardiol. Rep., 2016, 18(3), 25.
[] [PMID: 26841787]
Moodley, I. Review of the cardiovascular safety of COXIBs compared to NSAIDS. Cardiovasc. J. Afr., 2008, 19(2), 102-107.
[PMID: 18516356]
Ozbakir, B.; Crielaard, B.J.; Metselaar, J.M.; Storm, G.; Lammers, T. Liposomal corticosteroids for the treatment of inflammatory disorders and cancer. J. Control. Release, 2014, 190, 624-636.
[] [PMID: 24878183]
Rhen, T.; Cidlowski, J.A. Antiinflammatory action of glucocorticoids--new mechanisms for old drugs. N. Engl. J. Med., 2005, 353(16), 1711-1723.
[] [PMID: 16236742]
Smoak, K.A.; Cidlowski, J.A. Mechanisms of glucocorticoid receptor signaling during inflammation. Mech. Ageing Dev., 2004, 125(10-11), 697-706.
[] [PMID: 15541765]
Buttgereit, F.; Straub, R.H.; Wehling, M.; Burmester, G-R. Glucocorticoids in the treatment of rheumatic diseases: an update on the mechanisms of action. Arthritis Rheum., 2004, 50(11), 3408-3417.
[] [PMID: 15529366]
Dan, P.; Rosenblat, G.; Yedgar, S. Phospholipase A2 activities in skin physiology and pathology. Eur. J. Pharmacol., 2012, 691(1-3), 1-8.
[] [PMID: 22819703]
Scott, K.F.; Sajinovic, M.; Hein, J.; Nixdorf, S.; Galettis, P.; Liauw, W.; de Souza, P.; Dong, Q.; Graham, G.G.; Russell, P.J. Emerging roles for phospholipase A2 enzymes in cancer. Biochimie, 2010, 92(6), 601-610.
[] [PMID: 20362028]
Wang, H.; Klein, M.G.; Snell, G.; Lane, W.; Zou, H.; Levin, I.; Li, K.; Sang, B.C. Structure of human GIVD cytosolic phospholipase A2 reveals insights into substrate recognition. J. Mol. Biol., 2016, 428(13), 2769-2779.
[] [PMID: 27220631]
Kramer, R.M.; Checani, G.C.; Deykin, A.; Pritzker, C.R.; Deykin, D. Solubilization and properties of Ca2+-dependent human platelet phospholipase A2. Biochim. Biophys. Acta, 1986, 878(3), 394-403.
[] [PMID: 3756201]
Malley, K.R.; Koroleva, O.; Miller, I.; Sanishvili, R.; Jenkins, C.M.; Gross, R.W.; Korolev, S. The structure of IPLA 2 β reveals dimeric active sites and suggests mechanisms of regulation and localization. Nat. Commun., 2018, 9(1), 765.
[] [PMID: 29472584]
Mouchlis, V.D.; Limnios, D.; Kokotou, M.G.; Barbayianni, E.; Kokotos, G.; McCammon, J.A.; Dennis, E.A. Development of potent and selective inhibitors for group via calcium-independent phospholipase A2 guided by molecular dynamics and structure-activity relationships. J. Med. Chem., 2016, 59(9), 4403-4414.
[] [PMID: 27087127]
Murakami, M.; Taketomi, Y.; Miki, Y.; Sato, H.; Hirabayashi, T.; Yamamoto, K. Recent progress in phospholipase A2 research: from cells to animals to humans. Prog. Lipid Res., 2011, 50(2), 152-192.
[] [PMID: 21185866]
Hiraoka, M.; Abe, A.; Lu, Y.; Yang, K.; Han, X.; Gross, R.W.; Shayman, J.A. Lysosomal phospholipase A2 and phospholipidosis. Mol. Cell. Biol., 2006, 26(16), 6139-6148.
[] [PMID: 16880524]
Duncan, R.E.; Sarkadi-Nagy, E.; Jaworski, K.; Ahmadian, M.; Sul, H.S. Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J. Biol. Chem., 2008, 283(37), 25428-25436.
[] [PMID: 18614531]
Murakami, M.; Taketomi, Y.; Sato, H.; Yamamoto, K. Secreted phospholipase A2 revisited. J. Biochem., 2011, 150(3), 233-255.
[] [PMID: 21746768]
Mouchlis, V.D.; Chen, Y.; McCammon, J.A.; Dennis, E.A. Membrane allostery and unique hydrophobic sites promote enzyme substrate specificity. J. Am. Chem. Soc., 2018, 140(9), 3285-3291.
[] [PMID: 29342349]
Murakami, M.; Taketomi, Y. Secreted phospholipase A2 and mast cells. Allergol. Int., 2015, 64(1), 4-10.
[] [PMID: 25572553]
Leistad, L.; Feuerherm, A.J.; Faxvaag, A.; Johansen, B. Multiple phospholipase A2 enzymes participate in the inflammatory process in osteoarthritic cartilage. Scand. J. Rheumatol., 2011, 40(4), 308-316.
[] [PMID: 21417548]
De Luca, D.; Lopez-Rodriguez, E.; Minucci, A.; Vendittelli, F.; Gentile, L.; Stival, E.; Conti, G.; Piastra, M.; Antonelli, M.; Echaide, M.; Perez-Gil, J.; Capoluongo, E.D. Clinical and biological role of secretory phospholipase A2 in acute respiratory distress syndrome infants. Crit. Care, 2013, 17(4), R163.
[] [PMID: 23883784]
Yamamoto, K.; Isogai, Y.; Sato, H.; Taketomi, Y.; Murakami, M. Secreted phospholipase A2, lipoprotein hydrolysis, and atherosclerosis: integration with lipidomics. Anal. Bioanal. Chem., 2011, 400(7), 1829-1842.
[] [PMID: 21445663]
Yedgar, S.; Cohen, Y.; Shoseyov, D. Control of phospholipase A2 activities for the treatment of inflammatory conditions. Biochim. Biophys. Acta, 2006, 1761(11), 1373-1382.
[] [PMID: 16978919]
Dennis, E.A. Introduction to thematic review series: Phospholipases: Central role in lipid signaling and disease. J. Lipid Res., 2015, 56(7), 1245-1247.
[] [PMID: 26031662]
Margarucci, L.; Monti, M.C.; Chini, M.G.; Tosco, A.; Riccio, R.; Bifulco, G.; Casapullo, A. The inactivation mechanism of human group IIA phospholipase A(2) by Scalaradial. ChemBioChem, 2012, 13(15), 2259-2264.
[] [PMID: 23008213]
Jiang, J.; Neubauer, B.L.; Graff, J.R.; Chedid, M.; Thomas, J.E.; Roehm, N.W.; Zhang, S.; Eckert, G.J.; Koch, M.O.; Eble, J.N.; Cheng, L. Expression of group IIA secretory phospholipase A2 is elevated in prostatic intraepithelial neoplasia and adenocarcinoma. Am. J. Pathol., 2002, 160(2), 667-671.
[] [PMID: 11839587]
Pucer, A.; Brglez, V.; Payré, C.; Pungerčar, J.; Lambeau, G.; Petan, T.; Group, X. Group X secreted phospholipase A(2) induces lipid droplet formation and prolongs breast cancer cell survival. Mol. Cancer, 2013, 12(1), 111.
[] [PMID: 24070020]
Yagami, T.; Yamamoto, Y.; Koma, H. The role of secretory phospholipase A2 in the central nervous system and neurological diseases. Mol. Neurobiol., 2014, 49(2), 863-876.
[] [PMID: 24113843]
Yamashita, S.; Yamashita, J.; Ogawa, M. Overexpression of group II phospholipase A2 in human breast cancer tissues is closely associated with their malignant potency. Br. J. Cancer, 1994, 69(6), 1166-1170.
[] [PMID: 8198986]
Novo Belchor, M.; Hessel Gaeta, H.; Fabri Bittencourt Rodrigues, C.; Ramos da Cruz Costa, C.; de Oliveira Toyama, D.; Domingues Passero, L.F.; Dalastra Laurenti, M.; Hikari Toyama, M. Evaluation of rhamnetin as an inhibitor of the pharmacological effect of secretory phospholipase A2. Molecules, 2017, 22(9), 1441.
[] [PMID: 28858248]
Sales, T.A.; Marcussi, S.; da Cunha, E.F.F.; Kuca, K.; Ramalho, T.C. Can inhibitors of snake venom phospholipases A2 lead to new insights into anti-inflammatory therapy in humans? a theoretical study. Toxins (Basel), 2017, 9(11), 341.
[] [PMID: 29068410]
Ku, S-K.; Yang, E-J.; Kang, H.; Jung, B.; Bae, J-S. Inhibitory effect of polyozellin on secretory group IIA phospholipase A2. Arch. Pharm. Res., 2016, 39(2), 271-278.
[] [PMID: 26659873]
Ku, S-K.; Lee, H.G.; Bae, J-S. Inhibitory effect of baicalin, baicalein and wogonin on secretory group IIA phospholipase A2. Arch. Pharm. Res., 2015, 38(10), 1865-1872.
[] [PMID: 25564337]
Lee, I-C.; Bae, J-S. Inhibitory effect of vicenin-2 and scolymoside on secretory group IIA phospholipase A 2. Animal Cells Syst. (Seoul), 2015, 19(5), 305-311.
Lee, W.; Kwak, S.; Lee, H-S.; Na, D.H.; Lee, Y-M.; Bae, J-S. Inhibitory effect of exendin-4 on secretory group IIA phospholipase A2. Biochem. Biophys. Res. Commun., 2015, 459(4), 650-654.
[] [PMID: 25757907]
Bukhari, S.N.A.; Lauro, G.; Jantan, I.; Fei Chee, C.; Amjad, M.W.; Bifulco, G.; Sher, H.; Abdullah, I.; Rahman, N.A. Anti-inflammatory trends of new benzimidazole derivatives. Future Med. Chem., 2016, 8(16), 1953-1967.
[] [PMID: 27654499]
Jung, B.; Kim, J.; Bae, J-S. Dabrafenib, as a novel insight into drug repositioning against secretory group IIa phospholipase A2. Int. J. Pharmacol., 2016, 12(4), 415-421.
Gao, X.; Gong, H.; Men, P.; Zhou, L.; Ye, D. Design, synthesis, and biological evaluation of novel dual inhibitors of secretory phospholipase A2 and sphingomyelin synthase. Chin. J. Chem., 2013, 31(9), 1164-1170.
Dileep, K.V.; Remya, C.; Tintu, I.; Haridas, M.; Sadasivan, C. Interactions of selected indole derivatives with phospholipase A2: in silico and in vitro analysis. J. Mol. Model., 2013, 19(4), 1811-1817.
[] [PMID: 23315198]
Vasilakaki, S.; Barbayianni, E.; Magrioti, V.; Pastukhov, O.; Constantinou-Kokotou, V.; Huwiler, A.; Kokotos, G. Inhibitors of secreted phospholipase A2 suppress the release of PGE2 in renal mesangial cells. Bioorg. Med. Chem., 2016, 24(13), 3029-3034.
[] [PMID: 27234891]
Vasilakaki, S.; Pastukhov, O.; Mavromoustakos, T.; Huwiler, A.; Kokotos, G. Small peptides able to suppress prostaglandin E2 generation in renal mesangial cells. Molecules, 2018, 23(1), 158.
[] [PMID: 29342835]
Mouchlis, V.D.; Magrioti, V.; Barbayianni, E.; Cermak, N.; Oslund, R.C.; Mavromoustakos, T.M.; Gelb, M.H.; Kokotos, G. Inhibition of secreted phospholipases A2 by 2-oxoamides based on α-amino acids: Synthesis, in vitro evaluation and molecular docking calculations. Bioorg. Med. Chem., 2011, 19(2), 735-743.
[] [PMID: 21216150]
Mahalka, A.K.; Kinnunen, P.K. Class specific peptide inhibitors for secretory phospholipases A2. Biochem. Biophys. Res. Commun., 2013, 436(2), 349-353.
[] [PMID: 23747420]
Ye, L.; Dickerson, T.; Kaur, H.; Takada, Y.K.; Fujita, M.; Liu, R.; Knapp, J.M.; Lam, K.S.; Schore, N.E.; Kurth, M.J.; Takada, Y. Identification of inhibitors against interaction between pro-inflammatory sPLA2-IIA protein and integrin αvβ3. Bioorg. Med. Chem. Lett., 2013, 23(1), 340-345.
[] [PMID: 23164706]
Liao, C.; Sitzmann, M.; Pugliese, A.; Nicklaus, M.C. Software and resources for computational medicinal chemistry. Future Med. Chem., 2011, 3(8), 1057-1085.
[] [PMID: 21707404]
Rabal, O.; Urbano-Cuadrado, M.; Oyarzabal, J. Computational medicinal chemistry in fragment-based drug discovery: what, how and when. Future Med. Chem., 2011, 3(1), 95-134.
[] [PMID: 21428828]
Draheim, S.E.; Bach, N.J.; Dillard, R.D.; Berry, D.R.; Carlson, D.G.; Chirgadze, N.Y.; Clawson, D.K.; Hartley, L.W.; Johnson, L.M.; Jones, N.D.; McKinney, E.R.; Mihelich, E.D.; Olkowski, J.L.; Schevitz, R.W.; Smith, A.C.; Snyder, D.W.; Sommers, C.D.; Wery, J.P. Indole inhibitors of human nonpancreatic secretory phospholipase A2. 3. Indole-3-glyoxamides. J. Med. Chem., 1996, 39(26), 5159-5175.
[] [PMID: 8978844]
Kokotou, M.G.; Limnios, D.; Nikolaou, A.; Psarra, A.; Kokotos, G. Inhibitors of phospholipase A2 and their therapeutic potential: an update on patents (2012-2016). Expert Opin. Ther. Pat., 2017, 27(2), 217-225.
[] [PMID: 27718763]
Holmes, M.V.; Simon, T.; Exeter, H.J.; Folkersen, L.; Asselbergs, F.W.; Guardiola, M.; Cooper, J.A.; Palmen, J.; Hubacek, J.A.; Carruthers, K.F.; Horne, B.D.; Brunisholz, K.D.; Mega, J.L.; van Iperen, E.P.A.; Li, M.; Leusink, M.; Trompet, S.; Verschuren, J.J.W.; Hovingh, G.K.; Dehghan, A.; Nelson, C.P.; Kotti, S.; Danchin, N.; Scholz, M.; Haase, C.L.; Rothenbacher, D.; Swerdlow, D.I.; Kuchenbaecker, K.B.; Staines-Urias, E.; Goel, A.; van ’t Hooft, F.; Gertow, K.; de Faire, U.; Panayiotou, A.G.; Tremoli, E.; Baldassarre, D.; Veglia, F.; Holdt, L.M.; Beutner, F.; Gansevoort, R.T.; Navis, G.J.; Mateo Leach, I.; Breitling, L.P.; Brenner, H.; Thiery, J.; Dallmeier, D.; Franco-Cereceda, A.; Boer, J.M.A.; Stephens, J.W.; Hofker, M.H.; Tedgui, A.; Hofman, A.; Uitterlinden, A.G.; Adamkova, V.; Pitha, J.; Onland-Moret, N.C.; Cramer, M.J.; Nathoe, H.M.; Spiering, W.; Klungel, O.H.; Kumari, M.; Whincup, P.H.; Morrow, D.A.; Braund, P.S.; Hall, A.S.; Olsson, A.G.; Doevendans, P.A.; Trip, M.D.; Tobin, M.D.; Hamsten, A.; Watkins, H.; Koenig, W.; Nicolaides, A.N.; Teupser, D.; Day, I.N.M.; Carlquist, J.F.; Gaunt, T.R.; Ford, I.; Sattar, N.; Tsimikas, S.; Schwartz, G.G.; Lawlor, D.A.; Morris, R.W.; Sandhu, M.S.; Poledne, R.; Maitland-van der Zee, A.H.; Khaw, K.T.; Keating, B.J.; van der Harst, P.; Price, J.F.; Mehta, S.R.; Yusuf, S.; Witteman, J.C.M.; Franco, O.H.; Jukema, J.W.; de Knijff, P.; Tybjaerg-Hansen, A.; Rader, D.J.; Farrall, M.; Samani, N.J.; Kivimaki, M.; Fox, K.A.A.; Humphries, S.E.; Anderson, J.L.; Boekholdt, S.M.; Palmer, T.M.; Eriksson, P.; Paré, G.; Hingorani, A.D.; Sabatine, M.S.; Mallat, Z.; Casas, J.P.; Talmud, P.J. Secretory phospholipase A(2)-IIA and cardiovascular disease: a mendelian randomization study. J. Am. Coll. Cardiol., 2013, 62(21), 1966-1976.
[] [PMID: 23916927]
Ridker, P.M.; Lüscher, T.F. Anti-inflammatory therapies for cardiovascular disease. Eur. Heart J., 2014, 35(27), 1782-1791.
[] [PMID: 24864079]
Nicholls, S.J.; Kastelein, J.J.P.; Schwartz, G.G.; Bash, D.; Rosenson, R.S.; Cavender, M.A.; Brennan, D.M.; Koenig, W.; Jukema, J.W.; Nambi, V.; Wright, R.S.; Menon, V.; Lincoff, A.M.; Nissen, S.E. VISTA-16 investigators. Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial. JAMA, 2014, 311(3), 252-262.
[] [PMID: 24247616]
Lombardino, J.G.; Lowe, J.A., III The role of the medicinal chemist in drug discovery--then and now. Nat. Rev. Drug Discov., 2004, 3(10), 853-862.
[] [PMID: 15459676]
Ramalho, T.C.; de Castro, A.A.; Silva, D.R.; Silva, M.C.; Franca, T.C.C.; Bennion, B.J.; Kuca, K. Computational enzymology and organophosphorus degrading enzymes: Promising approaches toward remediation technologies of warfare agents and pesticides. Curr. Med. Chem., 2016, 23(10), 1041-1061.
[] [PMID: 26898655]
Wang, P.; Li, Y.; Shao, Q.; Zhou, W.; Wang, K. Targeting human secretory phospholipase A2 with designed peptide inhibitors for inflammatory therapy. J. Drug Target., 2015, 23(2), 140-146.
[] [PMID: 25237841]
Tamarit, B.; Theze, J. Use of indole-based compounds to induce or stimulate immune response to treat AIDS in HIVinfected subject, and suppress or reverse HIV-mediated immunodeficiency and restore cluster of differentiation 4 T cell function. WO2017037041-A1, 2017.
Luo, Ruixue Application of pleurolactone to preparation of drugs for treating inflammations 2016. CN105213371 (A)
Mehendale, H. M. Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (NIEHS), 2013. US 20130253060 A1
Dennis, E.A.; Kokotos, G.; Constantinou-kokotou, V.; David, S. Amides as inhibitors of human secreted phospholipase A2., 2014. US8759392B2.
Liu, J F Synthetic triterpenoid derivatives., 2012. WO2012027579-A1.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 19 February, 2020
Page: [477 - 497]
Pages: 21
DOI: 10.2174/0929867326666190201120646
Price: $65

Article Metrics

PDF: 63
PRC: 1