Abstract
Azaindoles have been accepted as important structures having various biological activities in medicinal chemistry in novel drug discovery. Various azaindole derivatives have been used commercially and newer analogues are synthesized continuously. As in literature, azaindole is a very potent moiety, its derivatives displayed a number of biological activities such as kinase inhibitors, cytotoxic agents, anti-angiogenic activity, CRTh2 receptor antagonists, melanin agonists, nicotine agonists, effectiveness in alzheimer disease, cytokinin analogs, Orai inhibitors in asthma and chemokine receptor- 2 (CCR2) antagonists. This review consists of biological activities of various azaindole analogs, reported so far, and their structure activity relations, along with future perspectives in this field.
Keywords: Azaindole, kinase inhibitor, orai inhibitor, cytotoxic agents, bioactive agents, anti-angiogenic activity.
Graphical Abstract
[1]
Florence, P.; Sylvain, R.; Benoît, J.; Jean, Y. Synthesis and reactivity of 7-azaindole (1H-pyrrolo [2,3-b]pyridine. Rev. Tetrahedron., 2007, 63(5), 1031-1064.
[2]
Hugon, F.B.; Bailly, C.; Golsteyn, R.M.; Pierré, A.; Léonce, S.; Hickman, J.; Pfeiffer, B.; Prudhomme, M. Synthesis and biological activities of isogranulatimide analogues. Bioorg. Med. Chem., 2007, 15(17), 5965-5980.
[3]
Marminon, C.; Pierre, A.; Pfeiffer, B.; Perez, V.; Leonce, S.; Joubert, A.; Bailly, C.; Renard, P.; Hickman, J.; Prudhomme, M. Syntheses and antiproliferative activities of 7-azarebec camycin analogues bearing one 7-azaindole moiety. J. Med. Chem., 2003, 46(4), 609-622.
[4]
Kelly, T.A.; McNeil, D.W.; Rose, J.M.; David, E.; Shih, C.K.; Grob, P.M. Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase 2-Indol-3-yl- and 2-azaindol-3-yl-dipyridodiazepinones. J. Med. Chem., 1997, 40(15), 2430-2433.
[5]
Shu-Bin, Z.; Suning, W. Luminescence and reactivity of 7-azaindole derivatives and complexes. Chem. Soc. Rev., 2010, 39, 3142-3156.
[6]
Chi, S.M.; Choi, J.K.; Yum, E.K.; Chi, D.Y. Palladium-catalyzed functionalization of 5- and 7-azaindoles. Tetrahedron Lett., 2000, 41, 919-922.
[7]
Levacher, V.; Benoit, R.; Duflos, J.; Dupas, G.; Bourguignon, J.; Queguigner, G. Broadening the scope of NADH models by using chiral and non-chiral pyrrolo [2,3-b] pyridine derivatives. Tetrahedron, 1991, 47, 429-440.
[8]
Guillard, J.; Decrop, M.; Gallay, N.; Espanel, C.; Boissier, E.; Herault, O.; Viaud-Massuard, M.C. Synthesis and biological evaluation of 7-azaindole derivatives, synthetic cytokinin analogues. Bioorg. Med. Chem. Lett., 2007, 17(7), 1934-1937.
[9]
Song, J.J.; Reeves, J.T.; Gallou, F.; Tan, Z.; Yee, N.K.; Senanayake, C.H. Organometallic methods for the synthesis and functionalization of azaindoles. Chem. Soc. Rev., 2007, 36(7), 1120-1132.
[10]
Lebouvier, N.; Pagniez, F.; Duflos, M.; LePape, P.; Na, Y.M.; Le, B.G.; Le, B.M. Synthesis and antifungal activities of new fluconazole analogues with azaheterocycle moiety. Bioorg. Med. Chem. Lett., 2007, 17(13), 3686-3689.
[11]
Anurag.; Roy, R.K.; Sharma, P.P. Synthesis and antiangiogenic activity of some novel Analogues of combretastatin. Int. J. Pharm. Tech. Res., 2009, 1(4), 1462-1469.
[13]
Mérour, J-Y.; Buron, F.; Plé, K.; Bonnet, P.; Routier, S. The azaindole framework in the design of kinase inhibitors. Molecules, 2014, 19, 19935-19979.
[14]
Robinson, M.M.; Robison, B.L. 7-Azaindole. I. Synthesis and conversion to 7-azatryptophan and other derivatives. J. Am. Chem. Soc., 1955, 77, 457-460.
[15]
Shen, T.Y.; Ellis, R.L.; Windholz, T.B.; Matzuk, A.R.; Rosegay, A.; Lucas, S.; Holly, F.W.; Wilson, A.N. Non-Steroid Anti-Inflammatory Agents. J. Am. Chem. Soc., 1963, 85, 488-489.
[16]
Paluchowska, M.H.; Dereń-Wesołek, A.; Mokrosz, J.L.; Charakchieva-Minol, S.; Chojnacka-Wójcik, E. Structure‐Activity relationship studies of CNS agents, Part 31[1]: Analogs of MP 3022 with a different number of nitrogen atoms in the heteroaromatic fragment—New 5‐HT1A Receptor ligands. Arch. Pharm., 1996, 329(10), 451-456.
[17]
Jean-Yves, M.; Benoît, J. Synthesis and Reactivity of 7-Azaindoles (1H-Pyrrolo(2,3-b)pyridine). Curr. Org. Chem., 2001, 5, 471-506.
[18]
Nemecek, C.; Metz, W.A.; Wentzler, S.; Ding, F.X.; Venot, C.; Souaille, C.; Dagallier, A.; Maignan, S.; Guilloteau, J.P.; Bernard, F. Design of potent IGF1-R inhibitors related to bis-azaindoles. Chem. Biol. Drug Des., 2010, 76, 100-106.
[19]
Lefoix, M.; Coudert, G.; Routier, S.; Pfeiffer, B.; Caignard, D-H.; Hickman, J.; Pierre, A.; Golsteyn, R.M.; Leonce, S.; Bossard, C.; Merour, J-Y. Novel 5-azaindolocarbazoles as cytotoxic agents and Chk1 inhibitors. Bioorg. Med. Chem., 2008, 16(9), 5303-5321.
[20]
Rekulapally, S.; Jarapula, R.; Gangarapu, K.; Manda, S.; Vaidya, J.R. Synthesis and anti-inflammatory activity of 2-substituted-((N, N-disubstituted)-1, 3-benzoxazole)-5-carboxamides. Med. Chem. Res., 2015, 24, 3412-3422.
[21]
Prudent, R.; Vassal-Stermann, E.; Nguyen, C.H.; Mollaret, M.; Viallet, J.; Desroches-Castan, A.; Martinez, A.; Barette, C.; Pillet, C.; Valdameri, G.; Soleilhac, E.; Di Pietro, A.; Feige, J.J.; Billaud, M.; Florent, J.C.; Lafanechère, L. Azaindole derivatives are inhibitors of microtubule dynamics, with anti-cancer and anti-angiogenic activities. Br. J. Pharmacol., 2013, 168(3), 673-685.
[22]
Sandham, D.A.; Adcock, C.; Bala, K.; Barker, L.; Brown, Z.; Dubois, G.; Budd, D. 7-Azaindole-3-acetic acid derivatives; potent and selective CRTh2 receptor antagonist. Bioorg. Med. Chem. Lett., 2009, 19, 4794-4798.
[23]
Murray, J.J.; Tonnel, A.B.; Brash, A.R.; Roberts, L.J.; Gosset, P.; Workman, R.; Capron, A.; Oates, J.A. Release of prostaglandin D2 into human airways during acute antigen challenge. N. Engl. J. Med., 1986, 315, 800-804.
[24]
Pettipher, R.; Hansel, T.T.; Armer, R. Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases. Nat. Rev. Drug Discov., 2007, 6, 313-325.
[25]
Lukacs, N.W.; Berlin, A.A.; Franz-Bacon, K.; Sasik, R.; Sprague, L.; Hardiman, G.; Boehme, S.; Bacon, A. CRTh2 antagonism significantly ameliorates airway hyperreactivity and downregulates inflammation-induced genes in a mouse model of airway inflammation. Am. J. Physiol., 2008, 295, 767-779.
[26]
Boehme, S.A.; Franz-Bacon, K.; Chen, E.P.; Sasik, R.; Sprague, L.J.; Ly, T.W.; Hardiman, G.; Bacon, K.B. A small molecule CRTH2 antagonist inhibits FITC-induced allergic cutaneous inflammation. Int. Immunol., 2009, 21(1), 81-93.
[27]
Pracharova, J.; Saltarella, T.; Muchova, T.R.; Scintilla, S. Novel antitumor cisplatin and transplatin derivatives containing 1-methyl-7-azaindole: Synthesis, characterization, and cellular responses. J. Med. Chem., 2015, 58(2), 847-859.
[28]
Page, J.D.; Husain, I.; Sancar, A.; Chaney, S.G. Effect of the diaminocyclohexane carrier ligand on platinum adduct formation,repair, and lethality. Biochemistry, 1990, 29, 1016-1024.
[29]
Kasparkova, J.; Marini, V.; Najajreh, Y.; Gibson, D.; Brabec, V. DNA binding mode of the cis and trans geometries of new antitumor nonclassical platinum complexes containing piperidine, piperazine or 4-picoline ligand in cell-free media Relations to their activity in cancer cell lines. Biochemistry, 2003, 42, 6321-6332.
[30]
Kasparkova, J.; Novakova, O.; Najajreh, Y.; Gibson, D.; Perez, J-M.; Brabec, V. Effects of a piperidine ligand on the mechanism of action of antitumor cisplatin. Chem. Res. Toxicol., 2003, 16, 1424-1432.
[31]
Wurtenberger, I.; Angermaier, B.; Kircher, B.; Gust, R. Synthesis and in vitro pharmacological behavior of platinum(II) complexes containing 1,2-diamino-1-(4-fluorophenyl)-2-alkanol ligands. J. Med. Chem., 2013, 56, 7951-7964.
[32]
Coluccia, M.; Natile, G. Trans-Platinum complexes in cancer therapy. Anticancer. Agents Med. Chem., 2007, 7, 111-123.
[33]
Aris, S.M.; Farrell, N.P. Towards antitumor active transplatinum compounds. Eur. J. Inorg. Chem., 2009, 10, 1293-1302.
[34]
Baltus, C.B.; Jorda, R.; Marot, C.; Berka, K.; Bazgier, V.; Krystof, V.; Pri, G.; Viaud-Massuard, M.C. Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors. Eur. J. Med. Chem., 2016, 108, 701-719.
[35]
Malumbres, M.; Barbacid, M. Mammalian cyclin-dependent kinases. Trends Biochem. Sci., 2005, 30, 630-641.
[36]
Senderowicz, A.M. Small molecule modulators of cyclin-dependent kinases for cancer therapy. Oncogene, 2000, 19, 6600-6606.
[37]
Lim, S.; Kaldis, P. Cdks, cyclins and CKIs: Roles beyond cell cycle regulation. Development, 2013, 140, 3079-3093.
[38]
Deshpande, A.; Sicinski, P.; Hinds, P.W. Cyclins and Cdks in development and cancer: A perspective. Oncogene, 2005, 24, 2909-2915.
[39]
Cincinelli, R.; Musso, L.; Merlini, L.; Giannini, G.; Vesci, L.; Ferdinando, M.; Carenini, N. 7-Azaindole-1-carboxamides as a new class of PARP-1 inhibitors. Bioorg. Med. Chem., 2014, 22, 1089-1103.
[40]
Wahlberg, E.; Karlberg, T.; Kouznetsova, E.; Markova, N.; Macchiarulo, A.; Thorsell, A.G.; Pol, E.; Frostell, A.; Ekblad, T.; Oncu, D.; Kull, B.; Robertson, G.M.; Pellicciari, R.; Schuler, H.; Weigelt, J. Family wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat. Biotechnol., 2012, 30, 283.
[41]
Javle, M.; Curtin, N. The role of PARP in DNA repair and therapeutic exploitation. Br. J. Cancer, 2011, 105, 1114-1122.
[42]
De Vos, M.; Schreiber, V.; Dantzer, F. The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art. Biochem. Pharmacol., 2012, 84, 137-146.
[43]
Powell, C.; Mikropoulos, C.; Kaye, S.B.; Nutting, C.M.; Bhide, S.A.; Newbold, K.; Harrington, K. Pre-clinical and clinical evaluation of PARP inhibitors as tumour-specific radiosensitisers. J. Cancer Treat. Rev., 2010, 36, 566-575.
[44]
Helleday, T. The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings. Mol. Oncol., 2011, 5, 387.
[45]
Ferraris, D.V. Increased PARP association with DNA alkylation damaged. J. Med. Chem., 2010, 53, 4561-4584.
[46]
Papeo, G.; Casale, E.; Montagnoli, A.; Cirla, A. PARP inhibitors in cancer therapy: An update. Expert Opin. Ther. Pat., 2013, 23, 503-514.
[47]
Jeanty, M.; Suzenet, F.; Delagrange, P.; Nosjean, O.; Boutin, J.A.; Caignard, D.H.; Guillaumet, G. Design and synthesis of 1-(2-alkanamidoethyl)-6-methoxy-7-azaindole derivatives as potent melatonin agonists. Bioorg. Med. Chem. Lett., 2011, 21, 2316-2319.
[48]
Reiter, R.J.; Tan, D.; Osuna, C.; Gitto, E. Actions of melatonin in the reduction of oxidative stress. Endocrinol. Rev, 2000, 7, 444-458.
[49]
Dubocovich, M.L.; Delagrange, P.; Krause, D.N.; Sugden Cardinali, D.; Olcese, D.P. Nomenclature, Classification, and Pharmacology of G Protein-Coupled melatonin receptors. J. Pharmacol. Rev, 2010, 62, 343-380.
[50]
Arendt, J. Melatonin: Characteristics, concerns, and prospects. J. Biol. Rhythms, 2005, 20, 291-303.
[51]
Barrenetxe, J.; Delagrange, P.; Martinez, J.A. Physiological and metabolic functions of melatonin. J. Physiol. Biochem., 2004, 60(1), 61-72.
[52]
Audinot, V.; Mailliet, F.; Lahaye-Brasseur, C.; Bonnaud, A.; Le Gall, A.; Amosse, C.; Dromaint, S.; Rodriguez, M.; Nagel, N.; Galizzi, J-P.; Malpaux, B.; Guillaumet, G.; Lesieur, D.; Lefoulon, F.; Renard, P.; Delagrange, P. Boutin. New selective ligands of human cloned melatonin MT1and MT2 receptors. Naunyn-Schmiedeberg’s J. A. Arch. Pharmacol, 2003, 367, 553-561.
[53]
Millan, M.J.; Gobert, A.; Lejeune, F.; Dekeyne, A.; Newman-Tancredi, A.; Pasteau, V.; Rivet, J-M.; Cussac, D. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J. Pharmacol. Exp. Ther., 2003, 306, 954-964.
[54]
Reppert, S.M.; Weaver, D.R.; Ebisawa, T. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron, 1994, 13, 1177-1185.
[55]
Dubocovich, M.L.; Delagrange, P.; Krause, D.N.; Sugden, D.; Cardinali, D.P.; Olcese, J. Melatonin changes the electrical spontaneous activity of hippocampal rat neurons at different ages. Pharmacol. Rev., 2010, 62, 343-380.
[56]
Esteve, C.; González, J.; Gual, S.; Vidal, L.; Alzina, S.; Sentellas, S.; Jover, I.; Horrillo, R.; De Alba, J. Discovery of 7-azaindole derivatives as potent orai inhibitors showing efficacy in a preclinical model of asthma. Bioorg. Med. Chem. Lett., 2015, 25, 1217-1222.
[57]
Oh-hora, M. Calcium signaling in the development and function of T‐lineage cells. Immunol. Rev., 2009, 231, 210.
[58]
Vig, M.; Peinelt, C.; Beck, A.; Koomoa, D.L.; Rabah, D.; Koblan-Huberson, M.; Kraft, S.; Turner, H.; Fleig, A.; Penner, R.; Kinet, J. CRACM1 Is a Plasma Membrane Protein Essential for Store-Operated Ca2+ Entry. Pac. Sci., 2006, 312, 1220-1223.
[59]
Vig, M.; De Haven, W.; Bird, G.S.; Billingsley, J.M.; Wang, H.; Rao, P.E.; Hutchings, A.B.; Jouvin, M-H.; Putney, J.W.; Kinet, J-P. Defective mast cell effector functions in mice lacking the CRACM1 pore subunit of store operated calcium release activated calcium channels. Nat. Immunol., 2008, 9(1), 89-96.
[60]
Parekh, A.B. Store-operated CRAC channels: Function in health and disease. Nat. Rev. Drug Discov., 2010, 9, 399-410.
[61]
Feske, S.; Ann, N.Y. Immunodeficiency due to defects in store‐operated calcium entry. Acad. Sci, 2011, 1238, 74-90.
[62]
Stoit, A.R.; Hartog, A.P.; Mons, H.; Schaik, S.V.; Barkhuijsen, N. 7-Azaindole derivatives as potential partial nicotinic agonists. Bioorg. Med. Chem. Lett., 2008, 18, 188-193.
[63]
Feneyrolles, C.; Guiet, L.; Singer, M.; Hijfte, N.V.; Cazals, B.D.; Fauvel, B.; Cheve, G.; Yasri, A. Discovering novel 7-azaindole-based series as potent AXL kinase inhibitors. Bioorg. Med. Chem. Lett., 2017, 27(4), 862-866.
[64]
Corno, C.; Gatti, L.; Lanzi, C.; Zaffaroni, N.; Colombo, D.; Perego, P. Role of the receptor tyrosine kinase AXL and its targeting in cancer cells. Curr. Med. Chem., 2016, 23, 1496-1512.
[65]
Sreenivasacharya, N.; Krotha, H.; Benderittera, P.; Hamela, A.; Variscoa, Y.; Hickmana, D.T.; Froestla, W.; Pfeifera, A.; Muhsa, A. Discovery and characterization of novel indole and 7-azaindole derivatives as inhibitors of β-amyloid-42 aggregation for the treatment of Alzheimer’s disease. Bioorg. Med. Chem. Lett., 2017, 27(6), 1405-1411.
[66]
Cazals, B.D.; Fauvel, B.; Singer, M.; Feneyrolles, C.; Bestgen, B.; Gassiot, F.; Spenlinhauer, A.; Warnault, P.; Hijfte, N.V.; Borjini, N.; Cheve, G.; Yasri, A. Rational design, synthesis, and biological evaluation of 7-azaindole derivatives as potent focused multi-targeted kinase inhibitors. J. Med. Chem., 2016, 59(8), 3886-3905.
[67]
Guillard, J.; Decrop, M.; Gallay, N.; Espanel, C.; Boissier, E.; Heraultb, O.; Massuard, M.C.V. Synthesis and biological evaluation of 7-azaindole derivatives, synthetic cytokinin analogues. Bioorg. Med. Chem. Lett., 2007, 17, 1934-1937.
[68]
Gummadi, V.R.; Rajagopalan, S.; Yeng, L.C.; Paydar, M.; Renukappa, G.A.; Ainan, B.R.; Krishnamurthy, N.R. Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode. Bioorg. Med. Chem. Lett., 2013, 23, 4911-4918.
[69]
Choi, Y.L.; Takeuchi, K.; Soda, M.; Inamura, K.; Togashi, Y.; Hatano, S.; Enomoto, M.; Hamada, T.; Haruta, H.; Watanabe, H.; Kurashina, K.; Hatanaka, H.; Ueno, T.; Takada, S.; Yamashita, Y.; Sugiyama, Y.; Ishikawa, Y.; Mano, H. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res., 2008, 68(13), 4971-4976.
[70]
Chiba, T.; Ohwada, J.; Sakamoto, H.; Kobayashi, T.; Fukami, T.A.; Irie, M.; Miura, T.; Ohara, K.; Koyano, H. Design and evaluation of azaindole-substituted N-hydroxypyridones as glyoxalase I inhibitors. Bioorg. Med. Chem. Lett., 2012, 22, 7486-7489.
[71]
Xia, M.; Hou, C.; DeMong, D.; Pollack, S.; Pan, M.; Singer, M.; Matheis, M.; Murray, W.; Cavender, D.; Wachter, M. Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists. Bioorg. Med. Chem. Lett., 2008, 18, 6468-6470.
[72]
Charo, I.F.; Myers, S.J.; Herman, A.; Franci, C.; Connolly, A.J.; Coughlin, S.R. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc. Natl. Acad. Sci., 1994, 91, 2752-2756.
[73]
Ruth, J.H.; Rottman, J.B.; Katschke, K.J.; Qin, S.; Wu, L.; LaRosa, G.; Ponath, P.; Pope, R.M.; Koch, A.E. Selective lymphocyte chemokine receptor expression in the rheumatoid joint. Arthritis Rheum., 2001, 44, 2750-2760.
[74]
Carulli, M.T.; Ponticos, V.H.; Xu, M.; Abraham, S.; Black, D.J.; Denton, C.M. Chemokine receptor CCR2 expression by systemic sclerosis fibroblasts: Evidence for autocrine regulation of myofibroblast differentiation. Arthritis Rheum., 2005, 52, 3772-3782.
[75]
Boring, L.; Gosling, J.; Cleary, M.; Charo, I. Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature, 1998, 394, 894-897.
[76]
Dawson, T.C.; Kuziel, W.A.; Osahar, T.A.; Maeda, N. Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis, 1999, 143, 205-211.
[77]
Weisberg, S.P.; Hunter, D.; Huber, R.; Lemieux, J.; Slaymaker, S.; Vaddi, K.; Charo, I.; Leibel, R.L.; Ferrante, A.W. CCR2 modulates inflammatory and metabolic effects of high-fat feeding. J. Clin. Invest., 2006, 116, 115-124.
[78]
Lloyd, C.M.; Minto, A.W.; Dorf, M.E.; Proudfoot, A.; Wells, T.N.; Salant, D.J.; Gutierrez-Ramos, J.C. Rantes and monocyte chemo attractant protein-1 (MCP-1) play an important role in the inflammatory phase of crescentic nephritis, but only MCP-1 is involved in crescent formation and interstitial fibrosis. J. Exp. Med., 1997, 185, 1371-1380.
[79]
Saify, Z.S.; Sultana, N.; Mushtaq, N.; Zaheer Ul Hasan, N. (1H-Pyrrolo [2,3-b] pyridine) 7-Azaindole derivatives and their Antiurease, Phosphodiesterase and glucuronidase Activity. Int. J. Biochem. Res. Rev., 2014, 4(6), 624-643.
[80]
Hugon, B.; Anizon, F.; Bailly, C.; Golsteyn, R.M.; Pierré, A.; Leonce, S.; Hickman, J.; Pfeiffer, B.; Prudhomme, M. Synthesis and biological activities of isogranulatimide analogues. Bioorg. Med. Chem., 2007, 15(17), 5965-5980.
[81]
Zafar, S.; Sultana, S.N.; Khan, A.; Haider, S. (1H-Pyrrolo [2,3-B] Pyridine) 7-Azaindole as Cholinesterase/ Glycation Inhibitors. Int. J. Biochem. Res. Rev., 2015, 8(1), 1-12.
Related Books
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Therapeutic Use of Plant Secondary Metabolites
Therapeutic Implications of Natural Bioactive Compounds
Frontiers in Bioactive Compounds
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Science of Spices and Culinary Herbs - Latest Laboratory, Pre-clinical, and Clinical Studies
Frontiers in Natural Product Chemistry
Frontiers in Natural Product Chemistry
Article Metrics
45
4