Medicinal Perspective of Indole Derivatives: Recent Developments and Structure-Activity Relationship Studies

Author(s): Devendra Kumar, Sahil Sharma, Sourav Kalra, Gurpreet Singh, Vikramdeep Monga, Bhupinder Kumar*

Journal Name: Current Drug Targets

Volume 21 , Issue 9 , 2020

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Graphical Abstract:


Abstract:

Heterocyclic compounds play a significant role in various biological processes of the human body and many of them are in clinical use due to their diverse, chemical and biological properties. Among these, indole is one of the most promising pharmacologically active molecules. Due to its chemical reactivity, indole has been willingly modified to obtain a variety of new lead molecules, which has been successfully utilized to obtained novel drug candidates for the treatment of different pharmacological diseases. Indole-based compounds such as vincristine (anticancer), reserpine (antihypertensive), amedalin (antidepressant) and many more describe the medicinal and pharmacological importance of the indole in uplifting human life. In this review, we compiled various reports on indole derivatives and their biological significance, including antifungal, antiprotozoal, antiplatelet, anti- Alzheimer’s, anti-Parkinson’s, antioxidant and anticancer potential from 2015 onwards. In addition, structure-activity relationship studies of the different derivatives have been included. We have also discussed novel synthetic strategies developed during this period for the synthesis of different indole derivatives. We believe that this review article will provide comprehensive knowledge about the medicinal importance of indoles and will help in the design and synthesis of novel indole-based molecules with high potency and efficacy.

Keywords: Indole derivatives, antifungal, antiprotozoal, anti-alzheimer's, anti-parkinson's, synthetic strategies.

[1]
Franzén RG. Recent advances in the preparation of heterocycles on solid support: a review of the literature. J Comb Chem 2000; 2(3): 195-214.
[http://dx.doi.org/10.1021/cc000002f] [PMID: 10827923]
[2]
Naim MJ, Alam O, Alam MJ, Bano F, Alam P, Shrivastava N. Recent review on indole: A privileged scaffold structure. Int J Pharm Sci Res 2016; 7: 51-62.
[3]
Dadashpour S, Emami S. Indole in the target-based design of anticancer agents: A versatile scaffold with diverse mechanisms. Eur J Med Chem 2018; 150: 9-29.
[http://dx.doi.org/10.1016/j.ejmech.2018.02.065] [PMID: 29505935]
[4]
Singh TP, Singh OM. Recent progress in biological activities of indole and indole alkaloids. Mini Rev Med Chem 2018; 18(1): 9-25.
[PMID: 28782480]
[5]
Radwanski ER, Last RL. Tryptophan biosynthesis and metabolism: biochemical and molecular genetics. Plant Cell 1995; 7(7): 921-34.
[PMID: 7640526]
[6]
Das B, Ravikanth B, Kumar AS, Kanth BS. An Efficient Procedure for the Synthesis of Substituted Pyridines Using KF• Al2O3. J Heterocycl Chem 2010; 46(6): 1208-12.
[http://dx.doi.org/10.1002/jhet.206]
[7]
Kaushik NK, Kaushik N, Attri P, et al. Biomedical importance of indoles. Molecules 2013; 18(6): 6620-62.
[http://dx.doi.org/10.3390/molecules18066620] [PMID: 23743888]
[8]
Ali NA, Dar BA, Pradhan V, Farooqui M, Farooqui M. Chemistry and biology of indoles and indazoles: a mini-review. Mini Rev Med Chem 2013; 13(12): 1792-800.
[http://dx.doi.org/10.2174/1389557511313120009] [PMID: 22625410]
[9]
Kumari A, Singh RK. Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg Chem 2019; 89103021
[http://dx.doi.org/10.1016/j.bioorg.2019.103021] [PMID: 31176854]
[10]
Sravanthi TV, Manju SL. Indoles - A promising scaffold for drug development. Eur J Pharm Sci 2016; 91: 1-10.
[http://dx.doi.org/10.1016/j.ejps.2016.05.025] [PMID: 27237590]
[11]
Wan Y, Li Y, Yan C, Yan M, Tang Z. Indole: A privileged scaffold for the design of anti-cancer agents. Eur J Med Chem 2019; 183111691
[http://dx.doi.org/10.1016/j.ejmech.2019.111691] [PMID: 31536895]
[12]
Rathi AK, Syed R, Singh V, Shin H-S, Patel RV. Kinase Inhibitor Indole Derivatives as Anticancer Agents: A Patent Review. Recent Patents Anticancer Drug Discov 2017; 12(1): 55-72.
[http://dx.doi.org/10.2174/1574892811666161003112119] [PMID: 27697069]
[13]
Chaudhary A, Pandeya SN, Kumar P, et al. Combretastatin a-4 analogs as anticancer agents. Mini Rev Med Chem 2007; 7(12): 1186-205.
[http://dx.doi.org/10.2174/138955707782795647] [PMID: 18220974]
[14]
Patil R, Patil SA, Beaman KD, Patil SA. Indole molecules as inhibitors of tubulin polymerization: potential new anticancer agents, an update (2013-2015). Future Med Chem 2016; 8(11): 1291-316.
[http://dx.doi.org/10.4155/fmc-2016-0047] [PMID: 27476704]
[15]
Patel H, Darji N, Pillai J, Patel B. Recent advance in anti-cancer activity of indole derivatives. Int J Drug Res Technol 2017; 2(3): 5.
[16]
El-sayed MT, Hamdy NA, Osman DA, Ahmed KM. Indoles as anticancer agents. Adv Mod Oncol Res 2015; 1(1): 20-35.
[http://dx.doi.org/10.18282/amor.v1.i1.12]
[17]
Singh Sidhu J, Singla R, Jaitak V. Indole derivatives as anticancer agents for breast cancer therapy: a review. Anti-Cancer Agent Med Chem 2016; 16(2): 160-73.
[http://dx.doi.org/10.2174/1871520615666150520144217]
[18]
Chadha N, Silakari O. Indoles as therapeutics of interest in medicinal chemistry: Bird’s eye view. Eur J Med Chem 2017; 134: 159-84.
[http://dx.doi.org/10.1016/j.ejmech.2017.04.003] [PMID: 28412530]
[19]
Chadha N, Silakari O. Indoles: As Multitarget Directed Ligands in Medicinal Chemistry.in Key Heterocycle Cores for Designing Multitargeting Molecules. Elsevier 2018; pp. 285-321.
[20]
Garg V, Maurya RK, Thanikachalam PV, Bansal G, Monga V. An insight into the medicinal perspective of synthetic analogs of indole: A review. Eur J Med Chem 2019; 180: 562-612.
[http://dx.doi.org/10.1016/j.ejmech.2019.07.019] [PMID: 31344615]
[21]
Zhang M-Z, Chen Q, Yang G-F. A review on recent developments of indole-containing antiviral agents. Eur J Med Chem 2015; 89: 421-41.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.065] [PMID: 25462257]
[22]
Phogat P, Singh P. A mini review on central nervous system potential of isatin derivatives. Cent Nerv Syst Agents Med Chem 2015; 15(1): 28-31.
[http://dx.doi.org/10.2174/1871524915666150213122246] [PMID: 25693647]
[23]
Batcho AD, Leimgruber W. Indoles from 2‐methylnitrobenzenes by condensation with formamide acetals followed by reduction: 4‐benzyloxyindole. Org Syn 1985; pp. 214-4.
[24]
Fischer E, Jourdan F. Ueber die hydrazine der brenztraubensäure. Ber Dtsch Chem Ges 1883; 16(2): 2241-5.
[http://dx.doi.org/10.1002/cber.188301602141]
[25]
Baudin J-B, Julia SA. Synthesis of indoles from N-aryl-1-alkenylsulphinamides. Tetrahedron Lett 1986; 27(7): 837-40.
[http://dx.doi.org/10.1016/S0040-4039(00)84114-3]
[26]
Reissert A. Einwirkung von oxalester und natriumäthylat auf nitrotoluole. synthese nitrirter phenylbrenztraubensäuren. Ber Dtsch Chem Ges 1897; 30(1): 1030-53.
[http://dx.doi.org/10.1002/cber.189703001200]
[27]
Baeyer A, Emmerling A. Synthese des indols. Ber Dtsch Chem Ges 1869; 2(1): 679-82.
[http://dx.doi.org/10.1002/cber.186900201268]
[28]
Gassman PG, Van Bergen T, Gruetzmacher G. Use of halogen-sulfide complexes in the synthesis of indoles, oxindoles, and alkylated aromatic amines. J Am Chem Soc 1973; 95(19): 6508-9.
[http://dx.doi.org/10.1021/ja00800a088]
[29]
Madelung W. Über eine neue darstellungsweise für substituierte indole. i. Ber Dtsch Chem Ges 1912; 45(1): 1128-34.
[http://dx.doi.org/10.1002/cber.191204501160]
[30]
Bischler A. Ueber die entstehung einiger substituirter indole. Ber Dtsch Chem Ges 1892; 25(2): 2860-79.
[http://dx.doi.org/10.1002/cber.189202502123]
[31]
Bartoli G, Palmieri G, Bosco M, Dalpozzo R. The reaction of vinyl Grignard reagents with 2-substituted nitroarenes: a new approach to the synthesis of 7-substituted indoles. Tetrahedron Lett 1989; 30(16): 2129-32.
[http://dx.doi.org/10.1016/S0040-4039(01)93730-X]
[32]
Hemetsberger H, Knittel D. Synthese und Thermolyse von α-Azidoacrylestern. Monatsh Chem 1972; 103(1): 194-204.
[http://dx.doi.org/10.1007/BF00912944]
[33]
Larock RC, Yum EK. Synthesis of indoles via palladium-catalyzed heteroannulation of internal alkynes. J Am Chem Soc 1991; 113(17): 6689-90.
[http://dx.doi.org/10.1021/ja00017a059]
[34]
Fukuyama T, Chen X, Peng G. A novel tin-mediated indole synthesis. J Am Chem Soc 1994; 116(7): 3127-8.
[http://dx.doi.org/10.1021/ja00086a054]
[35]
Acerbi A, Carfagna C, Costa M, Mancuso R, Gabriele B, Della Ca’ N. An Unprecedented Pd-Catalyzed Carbonylative Route to Fused Furo[3,4-b]indol-1-ones. Chemistry 2018; 24(19): 4835-40.
[http://dx.doi.org/10.1002/chem.201706067] [PMID: 29390167]
[36]
Heckman LM, He Z, Jamison TF. Synthesis of highly substituted 2-arylindoles via copper-catalyzed coupling of isocyanides and arylboronic acids. Org Lett 2018; 20(11): 3263-7.
[http://dx.doi.org/10.1021/acs.orglett.8b01132] [PMID: 29761699]
[37]
Krüll J, Hubert A, Nebel N, Prante O, Heinrich MR. Microwave-Assisted Rapid One-Pot Synthesis of Fused and Non-Fused Indoles and 5-[18 F]Fluoroindoles from Phenylazocarboxylates. Chemistry 2017; 23(64): 16174-8.
[http://dx.doi.org/10.1002/chem.201703890] [PMID: 28940808]
[38]
Lavekar AG, Equbal D, Sinha AK. Synergistic Cooperative Effect of Sodium borohydride‐Iodine Towards Cascade C− N and C− S/Se Bond Formation: One‐pot Regioselective Synthesis of 3‐Sulfenyl/selenyl Indoles and Mechanistic Insight. Adv Synth Catal 2018; 360(1): 180-5.
[http://dx.doi.org/10.1002/adsc.201701028]
[39]
Mizukami A, Ise Y, Kimachi T, Inamoto K. Rhodium-Catalyzed Cyclization of 2-Ethynylanilines in the Presence of Isocyanates: Approach toward Indole-3-carboxamides. Org Lett 2016; 18(4): 748-51.
[http://dx.doi.org/10.1021/acs.orglett.6b00007] [PMID: 26840978]
[40]
Yu S, Qi L, Hu K, et al. The Development of a palladium-catalyzed tandem addition/cyclization for the construction of indole skeletons. J Org Chem 2017; 82(7): 3631-8.
[http://dx.doi.org/10.1021/acs.joc.7b00148] [PMID: 28288278]
[41]
Pandolfi F, D’Acierno F, Bortolami M, et al. Searching for new agents active against Candida albicans biofilm: A series of indole derivatives, design, synthesis and biological evaluation. Eur J Med Chem 2019; 165: 93-106.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.012] [PMID: 30660829]
[42]
Han X-Y, Zhong Y-F, Li S-B, et al. Synthesis, characterization and antifungal evaluation of novel thiochromanone derivatives containing indole skeleton. Chem Pharm Bull (Tokyo) 2016; 64(9): 1411-6.
[http://dx.doi.org/10.1248/cpb.c16-00366] [PMID: 27373770]
[43]
Wu J-S, Zhang X, Zhang Y-L, Xie J-W. Synthesis and antifungal activities of novel polyheterocyclic spirooxindole derivatives. Org Biomol Chem 2015; 13(17): 4967-75.
[http://dx.doi.org/10.1039/C5OB00256G] [PMID: 25820179]
[44]
Bolous M, Arumugam N, Almansour AI, et al. Broad-spectrum antifungal activity of spirooxindolo-pyrrolidine tethered indole/imidazole hybrid heterocycles against fungal pathogens. Bioorg Med Chem Lett 2019; 29(16): 2059-63.
[http://dx.doi.org/10.1016/j.bmcl.2019.07.022] [PMID: 31320146]
[45]
Martins GM, do Carmo G, Morel AF, Kaufman TS, Silveira CC. A Convenient and Atom‐Economic One‐Pot Selenium‐Chloride‐Mediated Synthesis of 2‐Arylselenopheno [2, 3‐b] indoles and Their Antifungal Activity. Asian J Org Chem 2019; 8(3): 369-75.
[http://dx.doi.org/10.1002/ajoc.201900028]
[46]
Zheng S, Zhu R, Tang B, Chen L, Bai H, Zhang J. Synthesis and biological evaluations of a series of calycanthaceous analogues as antifungal agents. Nat Prod Res 2019; 1-9.
[http://dx.doi.org/10.1080/14786419.2019.1644635] [PMID: 31378086]
[47]
Mishra S, Kaur M, Chander S, et al. Rational modification of a lead molecule: Improving the antifungal activity of indole - triazole - amino acid conjugates. Eur J Med Chem 2018; 155: 658-69.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.039] [PMID: 29936353]
[48]
Shareef MA, Rajpurohit H, Sirisha K, et al. Design, Synthesis and Biological Evaluation of Substituted (1‐(4‐chlorobenzyl)‐1H‐indol‐3‐yl) 1H‐(1, 2, 3‐triazol‐4‐yl) methanones as Antifungal Agents. ChemistrySelect 2019; 4(8): 2258-66.
[http://dx.doi.org/10.1002/slct.201803572]
[49]
Tu J, Li Z, Jiang Y, et al. Discovery of Carboline Derivatives as Potent Antifungal Agents for the Treatment of Cryptococcal Meningitis. J Med Chem 2019; 62(5): 2376-89.
[http://dx.doi.org/10.1021/acs.jmedchem.8b01598] [PMID: 30753074]
[50]
Xu L-L, Hai P, Zhang S-B, et al. Prenylated Indole Diterpene Alkaloids from a Mine-Soil-Derived Tolypocladium sp. J Nat Prod 2019; 82(2): 221-31.
[http://dx.doi.org/10.1021/acs.jnatprod.8b00589] [PMID: 30702286]
[51]
Monjane J, Salamanca E, Giménez A, Sterner O. Novel Sulfur-Containing Indole from the Leaves of Clematis Viridiflora Bertol. Int J Res Pharm Biosci 2017; 4(2): 10-4.
[52]
De Gasparo R, Halgas O, Harangozo D, et al. Nanomolar Inhibitor of Trypanosoma brucei Trypanothione Reductase. Chemistry 2019; 25: 11416-21.
[http://dx.doi.org/10.1002/chem.201901664] [PMID: 31407832]
[53]
Farahat AA, Ismail MA, Kumar A, et al. Indole and benzimidazole bichalcophenes: Synthesis, DNA binding and antiparasitic activity. Eur J Med Chem 2018; 143: 1590-6.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.056] [PMID: 29126729]
[54]
Guillon J, Boudot C, Cohen A, et al. Synthesis of 1H-3-4-[(3-Dimethylaminopropyl) aminomethyl] phenyl-2-phenylindole and Evaluation of Its Antiprotozoal Activity. Molbank 2019; 2019(2): M1060.
[http://dx.doi.org/10.3390/M1060]
[55]
Pereira MDP, da Silva T, Aguiar ACC, et al. Chemical Composition, Antiprotozoal and Cytotoxic Activities of Indole Alkaloids and Benzofuran Neolignan of Aristolochia cordigera. Planta Med 2017; 83(11): 912-20.
[http://dx.doi.org/10.1055/s-0043-104776] [PMID: 28264205]
[56]
Porwal S, Gupta S, Chauhan PMS. gem-Dithioacetylated indole derivatives as novel antileishmanial agents. Bioorg Med Chem Lett 2017; 27(20): 4643-6.
[http://dx.doi.org/10.1016/j.bmcl.2017.09.018] [PMID: 28927767]
[57]
Muganza DM, Fruth B, Nzunzu JL, et al. In vitro antiprotozoal activity and cytotoxicity of extracts and isolated constituents from Greenwayodendron suaveolens. J Ethnopharmacol 2016; 193: 510-6.
[http://dx.doi.org/10.1016/j.jep.2016.09.051] [PMID: 27693770]
[58]
Kumar S, Bains T, Won Kim AS, et al. Highly potent 1H-1, 2, 3-triazole-tethered isatin-metronidazole conjugates against anaerobic foodborne, waterborne, and sexually-transmitted protozoal parasites. Front Cell Infect Microbiol 2018; 8: 380.
[http://dx.doi.org/10.3389/fcimb.2018.00380] [PMID: 30425970]
[59]
Gorki V, Singh R, Walter NS, Bagai U, Salunke DB. Synthesis and Evaluation of Antiplasmodial Efficacy of β-Carboline Derivatives against Murine Malaria. ACS Omega 2018; 3(10): 13200-10.
[http://dx.doi.org/10.1021/acsomega.8b01833] [PMID: 30411030]
[60]
Kunick C, Lande H, Gruenefeld J, Dzikowski R, Nasereddin A. New indole compounds having antiprotozoal activity and its use as well as methods for producing the same US Patents 2018
[61]
Sharma V, Jaiswal PK, Kumar K, et al. An efficient synthesis and biological evaluation of novel analogues of natural product Cephalandole A: A new class of antimicrobial and antiplatelet agents. Fitoterapia 2018; 129: 13-9.
[http://dx.doi.org/10.1016/j.fitote.2018.06.003] [PMID: 29894738]
[62]
Paliwal P, Chauhan G, Gautam D, Dash D, Patne SCU, Krishnamurthy S. Indole-3-carbinol improves neurobehavioral symptoms in a cerebral ischemic stroke model. Naunyn Schmiedebergs Arch Pharmacol 2018; 391(6): 613-25.
[http://dx.doi.org/10.1007/s00210-018-1488-2] [PMID: 29602953]
[63]
Mirfazli SS, Khoshneviszadeh M, Jeiroudi M, Foroumadi A, Kobarfard F, Shafiee A. Design, synthesis and QSAR study of arylidene indoles as anti-platelet aggregation inhibitors. Med Chem Res 2016; 25(1): 1-18.
[http://dx.doi.org/10.1007/s00044-015-1440-7] [PMID: 28111514]
[64]
Lee J, Lee W, Kim MA, Hwang JS, Na M, Bae JS. Inhibition of platelet aggregation and thrombosis by indole alkaloids isolated from the edible insect Protaetia brevitarsis seulensis (Kolbe). J Cell Mol Med 2017; 21(6): 1217-27.
[http://dx.doi.org/10.1111/jcmm.13055] [PMID: 27997749]
[65]
Haj Mohammad Ebrahim Tehrani K, Esfahani Zadeh M, Mashayekhi V, et al. Synthesis, antiplatelet activity and cytotoxicity assessment of indole-based hydrazone derivatives. Iran J Pharm Res 2015; 14(4): 1077-86.
[PMID: 26664374]
[66]
Yang C, Kwon S, Kim SJ, et al. Identification of indothiazinone as a natural antiplatelet agent. Chem Biol Drug Des 2017; 90(5): 873-82.
[http://dx.doi.org/10.1111/cbdd.13008] [PMID: 28432753]
[67]
Lee W, Lee J, Kulkarni R, et al. Antithrombotic and antiplatelet activities of small-molecule alkaloids from Scolopendra subspinipes mutilans. Sci Rep 2016; 6: 21956.
[http://dx.doi.org/10.1038/srep21956] [PMID: 26905699]
[68]
Kalhor N, Mardani M, Abdollahzadeh S, et al. Novel N‐Substituted ((1 H‐indol‐3‐yl) methylene) benzohydrazides and ((1 H‐indol‐3‐yl) methylene)‐2‐phenylhydrazines: Synthesis and Antiplatelet Aggregation Activity. Bull Korean Chem Soc 2015; 36(11): 2632-9.
[http://dx.doi.org/10.1002/bkcs.10531]
[69]
Aneja B, Arif R, Perwez A, et al. N‐Substituted 1, 2, 3‐Triazolyl‐Appended Indole‐Chalcone Hybrids as Potential DNA Intercalators Endowed with Antioxidant and Anticancer Properties. ChemistrySelect 2018; 3(9): 2638-45.
[http://dx.doi.org/10.1002/slct.201702913]
[70]
Nagarjuna U, Sravya G, Durgamma S, Padmaja A, Zyryanov GV. Synthesis of a new class of heteroaryl dipyrazolyl carbothioamides and heteroaryl dipyrazolyl thiazoles and evaluation as antioxidants. AIP Conference Proceedings. AIP Publishing. 2019.
[http://dx.doi.org/10.1063/1.5087371]
[71]
Asghari S, Pourshab M, Mohseni M. Synthesis, characterization, and evaluation of antioxidant and antibacterial activities of novel indole-hydrazono thiazolidinones. Monatsh Chem 2018; 149(12): 2327-36.
[http://dx.doi.org/10.1007/s00706-018-2292-x]
[72]
Demurtas M, Baldisserotto A, Lampronti I, et al. Indole derivatives as multifunctional drugs: Synthesis and evaluation of antioxidant, photoprotective and antiproliferative activity of indole hydrazones. Bioorg Chem 2019; 85: 568-76.
[http://dx.doi.org/10.1016/j.bioorg.2019.02.007] [PMID: 30825715]
[73]
Huang E, Zhang L, Xiao C, et al. Synthesis and biological evaluation of indole-3-carboxamide derivatives as antioxidant agents. Chin Chem Lett 2019.
[http://dx.doi.org/10.1016/j.cclet.2019.04.044]
[74]
Gurer-Orhan H, Karaaslan C, Ozcan S, et al. Novel indole-based melatonin analogues: Evaluation of antioxidant activity and protective effect against amyloid β-induced damage. Bioorg Med Chem 2016; 24(8): 1658-64.
[http://dx.doi.org/10.1016/j.bmc.2016.02.039] [PMID: 26970662]
[75]
Estevão MS, Carvalho LC, Ribeiro D, et al. Antioxidant activity of unexplored indole derivatives: synthesis and screening. Eur J Med Chem 2010; 45(11): 4869-78.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.059] [PMID: 20727623]
[76]
ElBordiny HS, El-Miligy MM, Kassab SE, Daabees H, Mohamed Ali WA, Abdelhamid Mohamed El-Hawash S. Design, synthesis, biological evaluation and docking studies of new 3-(4,5-dihydro-1H-pyrazol/isoxazol-5-yl)-2-phenyl-1H-indole derivatives as potent antioxidants and 15-lipoxygenase inhibitors. Eur J Med Chem 2018; 145: 594-605.
[http://dx.doi.org/10.1016/j.ejmech.2018.01.026] [PMID: 29339254]
[77]
Grozav A, Porumb I-D, Găină LI, Filip L, Hanganu D. Cytotoxicity and Antioxidant Potential of Novel 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole Derivatives. Molecules 2017; 22(2): 260.
[http://dx.doi.org/10.3390/molecules22020260] [PMID: 28208774]
[78]
Bhale PS, Chavan HV, Dongare SB, et al. Synthesis of extended conjugated indolyl chalcones as potent anti-breast cancer, anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett 2017; 27(7): 1502-7.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.052] [PMID: 28258796]
[79]
Zhou LY, Zhu Y, Jiang YR, Zhao XJ, Guo D. Design, synthesis and biological evaluation of dual acetylcholinesterase and phosphodiesterase 5A inhibitors in treatment for Alzheimer’s disease. Bioorg Med Chem Lett 2017; 27(17): 4180-4.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.013] [PMID: 28751142]
[80]
Vishnu MS, Pavankumar V, Kumar S, Raja AS. Experimental and Computational Evaluation of Piperonylic Acid Derived Hydrazones Bearing Isatin Moieties as Dual Inhibitors of Cholinesterases and Monoamine Oxidases. ChemMedChem 2019; 14(14): 1359-76.
[http://dx.doi.org/10.1002/cmdc.201900277] [PMID: 31177620]
[81]
Purgatorio R, de Candia M, Catto M, et al. Investigating 1,2,3,4,5,6-hexahydroazepino[4,3-b]indole as scaffold of butyrylcholinesterase-selective inhibitors with additional neuroprotective activities for Alzheimer’s disease. Eur J Med Chem 2019; 177: 414-24.
[http://dx.doi.org/10.1016/j.ejmech.2019.05.062] [PMID: 31158754]
[82]
Marcinkowska M, Bucki A, Panek D, et al. Anti-Alzheimer’s multitarget-directed ligands with serotonin 5-HT6 antagonist, butyrylcholinesterase inhibitory, and antioxidant activity. Arch Pharm (Weinheim) 2019; 352(7)e1900041
[http://dx.doi.org/10.1002/ardp.201900041] [PMID: 31162703]
[83]
Denya I, Malan SF, Enogieru AB, et al. Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer’s disease. MedChemComm 2018; 9(2): 357-70.
[http://dx.doi.org/10.1039/C7MD00569E] [PMID: 30108930]
[84]
Benek O, Soukup O, Pasdiorova M, et al. Design, Synthesis and in vitro Evaluation of Indolotacrine Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer’s Disease. ChemMedChem 2016; 11(12): 1264-9.
[http://dx.doi.org/10.1002/cmdc.201500383] [PMID: 26427608]
[85]
Pisani L, De Palma A, Giangregorio N, et al. Mannich base approach to 5-methoxyisatin 3-(4-isopropylphenyl)hydrazone: A water-soluble prodrug for a multitarget inhibition of cholinesterases, beta-amyloid fibrillization and oligomer-induced cytotoxicity. Eur J Pharm Sci 2017; 109: 381-8.
[http://dx.doi.org/10.1016/j.ejps.2017.08.004] [PMID: 28801274]
[86]
Lalut J, Santoni G, Karila D, et al. Novel multitarget-directed ligands targeting acetylcholinesterase and σ1 receptors as lead compounds for treatment of Alzheimer’s disease: Synthesis, evaluation, and structural characterization of their complexes with acetylcholinesterase. Eur J Med Chem 2019; 162: 234-48.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.064] [PMID: 30447434]
[87]
Patel DV, Patel NR, Kanhed AM, et al. Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents. ACS Chem Neurosci 2019; 10(8): 3635-61.
[http://dx.doi.org/10.1021/acschemneuro.9b00226] [PMID: 31310717]
[88]
Rahmani-Khajouei M, Mohammadi-Farani A, Ghorbani H, Aliabadi A. Synthesis and Acetylcholinesterase Inhibitory Assessment of 3-(2-(4-benzoylpiperazin-1-yl) ethylimino) indolin-2-one Derivatives with Potential Anti-Alzheimer Effects. J Rep Pharm Sci 2015; 4(2): 148-57.
[89]
Cheng K, Li S, Lv X, et al. Design, synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure. Bioorg Med Chem Lett 2019; 29(8): 1012-8.
[http://dx.doi.org/10.1016/j.bmcl.2019.02.008] [PMID: 30792039]
[90]
Nam M-H, Park M, Park H, et al. Indole-substituted benzothiazoles and benzoxazoles as selective and reversible MAO-B inhibitors for treatment of Parkinson’s disease. ACS Chem Neurosci 2017; 8(7): 1519-29.
[http://dx.doi.org/10.1021/acschemneuro.7b00050] [PMID: 28332824]
[91]
Tavari M, Malan SF, Joubert J. Design, synthesis, biological evaluation and docking studies of sulfonyl isatin derivatives as monoamine oxidase and caspase-3 inhibitors. MedChemComm 2016; 7(8): 1628-39.
[http://dx.doi.org/10.1039/C6MD00228E]
[92]
Takao K, U S, Kamauchi H, Sugita Y. Design, synthesis and evaluation of 2-(indolylmethylidene)-2,3-dihydro-1-benzofuran-3-one and 2-(indolyl)-4H-chromen-4-one derivatives as novel monoamine oxidases inhibitors. Bioorg Chem 2019; 87: 594-600.
[http://dx.doi.org/10.1016/j.bioorg.2019.03.042] [PMID: 30933784]
[93]
Sasidharan R, Manju SL, Uçar G, Baysal I, Mathew B. Identification of Indole-Based Chalcones: Discovery of a Potent, Selective, and Reversible Class of MAO-B Inhibitors. Arch Pharm (Weinheim) 2016; 349(8): 627-37.
[http://dx.doi.org/10.1002/ardp.201600088] [PMID: 27373997]
[94]
Bommagani S, Ponder J, Penthala NR, et al. Indole carboxylic acid esters of melampomagnolide B are potent anticancer agents against both hematological and solid tumor cells. Eur J Med Chem 2017; 136: 393-405.
[http://dx.doi.org/10.1016/j.ejmech.2017.05.031] [PMID: 28525840]
[95]
Singh A, Raghuwanshi K, Patel VK, et al. Assessment of 5-substituted isatin as surface recognition group: design, synthesis, and antiproliferative evaluation of hydroxamates as novel histone deacetylase inhibitors. Pharm Chem J 2017; 51(5): 366-74.
[http://dx.doi.org/10.1007/s11094-017-1616-1]
[96]
Huong TT, Dung DT, Huan NV, et al. Novel N-hydroxybenzamides incorporating 2-oxoindoline with unexpected potent histone deacetylase inhibitory effects and antitumor cytotoxicity. Bioorg Chem 2017; 71: 160-9.
[http://dx.doi.org/10.1016/j.bioorg.2017.02.002] [PMID: 28196602]
[97]
Çetin İ, Elma PE, Topçul M, Karalı N. Anticancer activities and cell death mechanisms of 1H-indole-2, 3-dione 3-[N-(4 sulfamoylphenyl) thiosemicarbazone] derivatives. Istanbul J Pharm 2018; 48(3): 63-7.
[http://dx.doi.org/10.26650/IstanbulJPharm.2018.414805]
[98]
Eldehna WM, Abo-Ashour MF, Nocentini A, et al. Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies. Eur J Med Chem 2017; 139: 250-62.
[http://dx.doi.org/10.1016/j.ejmech.2017.07.073] [PMID: 28802125]
[99]
Ibrahim HS, Abou-Seri SM, Tanc M, Elaasser MM, Abdel-Aziz HA, Supuran CT. Isatin-pyrazole benzenesulfonamide hybrids potently inhibit tumor-associated carbonic anhydrase isoforms IX and XII. Eur J Med Chem 2015; 103: 583-93.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.021] [PMID: 26408817]
[100]
Jain R, Gahlyan P, Dwivedi S, et al. Design, Synthesis and Evaluation of 1H‐1, 2, 3‐Triazol‐4‐yl‐methyl Tethered 3‐Pyrrolylisatins as Potent Anti‐Breast Cancer Agents. ChemistrySelect 2018; 3(19): 5263-8.
[http://dx.doi.org/10.1002/slct.201800420]
[101]
Debnath B, Ganguly S. Synthesis, biological evaluation, in silico docking, and virtual ADME studies of 2-[2-Oxo-3-(arylimino) indolin-1-yl]-N-arylacetamides as potent anti-breast cancer agents. Monatsh Chem 2016; 147(3): 565-74.
[http://dx.doi.org/10.1007/s00706-015-1566-9]
[102]
Singh H, Singh JV, Gupta MK, et al. Triazole tethered isatin-coumarin based molecular hybrids as novel antitubulin agents: Design, synthesis, biological investigation and docking studies. Bioorg Med Chem Lett 2017; 27(17): 3974-9.
[http://dx.doi.org/10.1016/j.bmcl.2017.07.069] [PMID: 28797799]
[103]
Sultana F, Shaik SP, Nayak VL, et al. Design, Synthesis and Biological Evaluation of 2‐Anilinopyridyl‐Linked Oxindole Conjugates as Potent Tubulin Polymerisation Inhibitors. ChemistrySelect 2017; 2(31): 9901-10.
[http://dx.doi.org/10.1002/slct.201701787]
[104]
Deeva OA, Pantileev AS, Rybina IV, Yarkova MA, Gudasheva TA, Seredenin SB. A Novel Dipeptide Ligand of TSPO. Dokl Biochem Biophys 2019; 484(1): 17-20.
[http://dx.doi.org/10.1134/S1607672919010046] [PMID: 31012004]
[105]
Jupally VR, Eggadi V, Sheshagiri SBB, Kulandaivelu U. Synthesis and evaluation of neuropharmacological profile of isatin-3-[N2-(2-benzalaminothiazol-4-yl)] hydrazones. Egypt Pharmaceuti J 2015; 14(2): 130.
[http://dx.doi.org/10.4103/1687-4315.161287]
[106]
Lima-Maximino MG, Cueto-Escobedo J, Rodríguez-Landa JF, Maximino C. FGIN-1-27, an agonist at translocator protein 18 kDa (TSPO), produces anti-anxiety and anti-panic effects in non-mammalian models. Pharmacol Biochem Behav 2018; 171: 66-73.
[http://dx.doi.org/10.1016/j.pbb.2018.04.007] [PMID: 29698632]
[107]
Sunke R, Bankala R, Thirupataiah B, et al. InCl3 mediated heteroarylation of indoles and their derivatization via CH activation strategy: Discovery of 2-(1H-indol-3-yl)-quinoxaline derivatives as a new class of PDE4B selective inhibitors for arthritis and/or multiple sclerosis. Eur J Med Chem 2019; 174: 198-215.
[http://dx.doi.org/10.1016/j.ejmech.2019.04.020] [PMID: 31035240]
[108]
Kaur M, Singh M, Silakari O. Oxindole-based SYK and JAK3 dual inhibitors for rheumatoid arthritis: designing, synthesis and biological evaluation. Future Med Chem 2017; 9(11): 1193-211.
[http://dx.doi.org/10.4155/fmc-2017-0037] [PMID: 28722479]
[109]
Chen H, Yang H, Wang Z, Xie X, Nan F. Discovery of 3-Substituted 1H-Indole-2-carboxylic Acid Derivatives as a Novel Class of CysLT1 Selective Antagonists. ACS Med Chem Lett 2016; 7(3): 335-9.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00482] [PMID: 26985325]
[110]
Bhat MA, Al-Omar MA, Raish M, et al. Indole derivatives as cyclooxygenase inhibitors: synthesis, biological evaluation and docking studies. Molecules 2018; 23(6): 1250.
[http://dx.doi.org/10.3390/molecules23061250] [PMID: 29882911]
[111]
Jaisankar P, Swarnakar S, Chatterjee S, Verma S, Mandal M, Chaudhuri SR. 3-indolyl furanoids as inhibitors of matrix metalloproteinase- 9 for prevention of gastric ulcer and other inflammatory diseases US Patents 2018


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VOLUME: 21
ISSUE: 9
Year: 2020
Published on: 28 July, 2020
Page: [864 - 891]
Pages: 28
DOI: 10.2174/1389450121666200310115327
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