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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Mini-Review Article

Therapeutic Potential of Indole Derivatives as Anti-HIV Agents: A Mini-review

Author(s): Qingtai Chen, Chongchong Wu*, Jinjin Zhu, Enzhong Li and Zhi Xu*

Volume 22, Issue 12, 2022

Published on: 12 October, 2021

Page: [993 - 1008] Pages: 16

DOI: 10.2174/1568026621666211012111901

Price: $65

Abstract

Acquired immunodeficiency syndrome (AIDS), caused by the human immunodeficiency virus (HIV), is one of the leading causes of human deaths. The advent of different anti-HIV drugs has turned AIDS/HIV from a deadly infection to chronic and manageable disease. However, the development of multidrug-resistant viruses, along with the severe side effects of anti-HIV agents, has compromised their efficacy and limited the treatment options. Indoles, the most common frameworks in the bioactive molecules, represent attractive scaffolds for designing and developing novel drugs. Indole derivatives are potent inhibitors of HIV enzymes such as reverse transcriptase, integrase, and protease. Furthermore, some indole-based agents, like delavirdine, have already been applied in clinics or are under clinical evaluations for the treatment of AIDS/HIV, revealing that indole moiety is a useful template for the development of anti-HIV agents. This review focuses on the recent advancement in indole derivatives, including indole alkaloids, hybrids, and dimers with anti-HIV potential, covering articles published between 2010 and 2020. The chemical structures, structure-activity relationship, and mechanisms of action are also discussed.

Keywords: Indole, Alkaloids, Hybrid compounds, Dimers, HIV, AIDS, Drug resistance, Structure-activity relationship.

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Curr Top Med Chem Motati D.R. 19 1650 2019 10.2174/1568026619666190717163959 Motati D.R.; Uredi D.; Watkins E.B.; The discovery and development of oxalamide and pyrrole small molecule inhibitors of gp120 and HIV entry-A review. Curr Top Med Chem 2019,19(18),1650-1675 Lancet Ghosn J. 392 685 2018 10.1016/S0140-6736(18)31311-4 Ghosn J.; Taiwo B.; Seedat S.; Autran B.; Katlama C.; HIV. Lancet 2018,392(10148),685-697 Curr Top Med Chem Voshavar C. 19 1571 2019 10.2174/1568026619666190619115243 Voshavar C.; Protease inhibitors for the treatment of HIV/AIDS: Recent advances and future challenges. Curr Top Med Chem 2019,19(18),1571-1598 Arch Pharm (Weinheim) Wang R. 352 e1900045 2019 10.1002/ardp.201900045 Wang R.; Xu K.; Shi W.; Quinolone derivatives: Potential anti-HIV agent-development and application. Arch Pharm (Weinheim) 2019,352(9),e1900045 World Health Organization. Number of people (all ages) living with HIV estimates by WHO region. https://apps.who.int/gho/data/view.main.22100WHO?lang=en2019 Curr Top Med Chem Maeda K. 19 1621 2019 10.2174/1568026619666190712204603 Maeda K.; Das D.; Kobayakawa T.; Tamamura H.; Takeuchi H.; Discovery and development of anti-HIV therapeutic agents: Progress towards improved HIV medication. Curr Top Med Chem 2019,19(18),1621-1649 Curr Infect Dis Rep Gravatt L.A.H. 19 42 2017 10.1007/s11908-017-0601-x Gravatt L.A.H.; Leibrand C.R.; Patel S.; McRae M.; New drugs in the pipeline for the treatment of HIV: A review. Curr Infect Dis Rep 2017,19(11),42 Med Res Rev Battini L. 39 1235 2019 10.1002/med.21544 Battini L.; Bollini M.; Challenges and approaches in the discovery of human immunodeficiency virus type-1 non-nucleoside reverse transcriptase inhibitors. Med Res Rev 2019,39(4),1235-1273 Eur J Med Chem Gill M.S.A. 179 423 2019 10.1016/j.ejmech.2019.06.058 Gill M.S.A.; Hassan S.S.; Ahemad N.; Evolution of HIV-1 reverse transcriptase and integrase dual inhibitors: Recent advances and developments. Eur J Med Chem 2019,179,423-448 Mini Rev Med Chem Singh T.P. 18 9 2018 Singh T.P.; Singh O.M.; Recent progress in biological activities of indole and indole alkaloids. Mini Rev Med Chem 2018,18(1),9-25 Bioorg Chem Kumari A. 89 103021 2019 10.1016/j.bioorg.2019.103021 Kumari A.; Singh R.K.; Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg Chem 2019,89,103021 Eur J Med Chem Zhang M.Z. 89 421 2015 10.1016/j.ejmech.2014.10.065 Zhang M.Z.; Chen Q.; Yang G.F.; A review on recent developments of indole-containing antiviral agents. Eur J Med Chem 2015,89,421-441 Eur J Pharm Sci Sravanthi T.V. 91 1 2016 10.1016/j.ejps.2016.05.025 Sravanthi T.V.; Manju S.L.; Indoles - A promising scaffold for drug development. Eur J Pharm Sci 2016,91,1-10 Anticancer Agents Med Chem Kaur K. 19 962 2019 10.2174/1871520619666190312125602 Kaur K.; Jaitak V.; Recent development in indole derivatives as anticancer agents for breast cancer. Anticancer Agents Med Chem 2019,19(8),962-983 Eur J Med Chem Garg V. 180 562 2019 10.1016/j.ejmech.2019.07.019 Garg V.; Maurya R.K.; Thanikachalam P.V.; 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 Eur J Med Chem Qin H.L. 194 112245 2020 10.1016/j.ejmech.2020.112245 Qin H.L.; Liu J.; Fang W.Y.; Ravindar L.; Rakesh K.P.; Indole-based derivatives as potential antibacterial activity against methicillin-resistance Staphylococcus aureus (MRSA). Eur J Med Chem 2020,194,112245 Tetrahedron Lett Ciulla M.G. 59 3223 2018 10.1016/j.tetlet.2018.07.045 Ciulla M.G.; Kumar K.; The natural and synthetic indole weaponry against bacteria. Tetrahedron Lett 2018,59,3223-3233 Eur J Med Chem Jia Y. 200 112359 2020 10.1016/j.ejmech.2020.112359 Jia Y.; Wen X.; Gong Y.; Wang X.; Current scenario of indole derivatives with potential anti-drug-resistant cancer activity. Eur J Med Chem 2020,200,112359 Eur J Med Chem Wan Y. 183 111691 2019 10.1016/j.ejmech.2019.111691 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 2019,183,111691 J Heterocycl Chem Jiang D. 55 1263 2018 10.1002/jhet.3189 Jiang D.; Wang G.Q.; Liu X.; Zhang Z.; Feng L.S.; Liu M.L.; Isatin derivatives with potential antitubercular activities. J Heterocycl Chem 2018,55,1263-1279 Chin Chem Lett Xu Z. 28 159 2017 10.1016/j.cclet.2016.07.032 Xu Z.; Zhang S.; Gao C.; Fan J.; Zhao F.; Lv Z.S.; Feng L.S.; Isatin hybrids and their anti-tuberculosis activity. Chin Chem Lett 2017,28(2),159-167 ACS Infect Dis Ye N. 2 382 2016 10.1021/acsinfecdis.6b00041 Ye N.; Chen H.; Wold E.A.; Shi P.Y.; Zhou J.; Therapeutic potential of spirooxindoles as antiviral agents. ACS Infect Dis 2016,2(6),382-392 Eur J Med Chem Chadha N. 134 159 2017 10.1016/j.ejmech.2017.04.003 Chadha N.; Silakari O.; Indoles as therapeutics of interest in medicinal chemistry: Bird’s eye view. Eur J Med Chem 2017,134,159-184 Antivir Chem Chemother Famiglini V. 26 2040206617753443 2018 10.1177/2040206617753443 Famiglini V.; Silvestri R.; Indolylarylsulfones, a fascinating story of highly potent human immunodeficiency virus type 1 non-nucleoside reverse transcriptase inhibitors. Antivir Chem Chemother 2018,26,2040206617753443 J Med Chem Di Santo R. 57 539 2014 10.1021/jm400674a Di Santo R.; Inhibiting the HIV integration process: past, present, and the future. J Med Chem 2014,57(3),539-566 Drugs Scott L.J. 60 1411 2000 10.2165/00003495-200060060-00013 Scott L.J.; Perry C.M.; Delavirdine: a review of its use in HIV infection. Drugs 2000,60(6),1411-1444 Drug Discov Today Abdou M.M. 24 916 2019 10.1016/j.drudis.2018.11.016 Abdou M.M.; O’Neill P.M.; Amigues E.; Matziari M.; Phosphinic acids: current status and potential for drug discovery. Drug Discov Today 2019,24(3),916-929 Curr Med Chem Zhou X. 20 953 2013 Zhou X.; Liu J.; Yang B.; Lin X.; Yang X.W.; Liu Y.; Marine natural products with anti-HIV activities in the last decade. Curr Med Chem 2013,20(7),953-973 Nat Prod Rep Singh I.P. 27 1781 2010 10.1039/c0np00025f Singh I.P.; Bodiwala H.S.; Recent advances in anti-HIV natural products. Nat Prod Rep 2010,27(12),1781-1800 Mini Rev Med Chem Singh T.P. 18 9 2018 Singh T.P.; Singh O.M.; Mukherjee Recent progress in biological activities of indole and indole alkaloids. Mini Rev Med Chem 2018,18(1),9-25 J Antibiot (Tokyo) He F. 65 109 2012 10.1038/ja.2011.117 He F.; Sun Y.L.; Liu K.S.; Zhang X.Y.; Qian P.Y.; Wang Y.F.; Qi S.H.; Indole alkaloids from marine-derived fungus Aspergillus syd-owii SCSIO 00305. J Antibiot (Tokyo) 2012,65(2),109-111 Fitoterapia Rosales P.F. 143 104558 2020 10.1016/j.fitote.2020.104558 Rosales P.F.; Bordin G.S.; Gower A.E.; Moura S.; Indole alkaloids: 2012 until now, highlighting the new chemical structures and bio-logical activities. Fitoterapia 2020,143,104558 Mini Rev Med Chem Novanna M. 19 194 2019 10.2174/1389557518666181102110537 Novanna M.; Ethiraj K.R.; Kannadasan S.; An overview of synthesis of indole alkaloids and biological activities of secondary metabo-lites isolated from hyrtios species. Mini Rev Med Chem 2019,19(3),194-205 Bioorg Chem Liu Y.P. 83 1 2019 10.1016/j.bioorg.2018.10.013 Liu Y.P.; Liu Q.L.; Zhang X.L.; Niu H.Y.; Guan C.Y.; Sun F.K.; Xu W.; Fu Y.H.; Bioactive monoterpene indole alkaloids from Nau-clea officinalis. Bioorg Chem 2019,83,1-5 Org Lett Tan C.J. 12 2370 2010 10.1021/ol100715x Tan C.J.; Di Y.T.; Wang Y.H.; Zhang Y.; Si Y.K.; Zhang Q.; Gao S.; Hu X.J.; Fang X.; Li S.F.; Hao X.J.; Three new indole alkaloids from Trigonostemon lii. Org Lett 2010,12(10),2370-2373 J Nat Prod Zhang D. 80 371 2017 10.1021/acs.jnatprod.6b00829 Zhang D.; Zhao L.; Wang L.; Fang X.; Zhao J.; Wang X.; Li L.; Liu H.; Wei Y.; You X.; Cen S.; Yu L.; Griseofulvin derivative and indole alkaloids from Penicillium griseofulvum CPCC 400528. J Nat Prod 2017,80(2),371-376 Phytother Res Kumari A. 29 840 2015 10.1002/ptr.5318 Kumari A.; Baskaran P.; Van Staden J.; Enhanced HIV-1 reverse transcriptase inhibitory and antibacterial properties in callus of Catha edulis Forsk. Phytother Res 2015,29(6),840-843 Chem Biodivers Zhu H. 12 1547 2015 10.1002/cbdv.201400412 Zhu H.; Chen C.; Wang J.; Li X.N.; Wei G.; Guo Y.; Yao G.; Luo Z.; Zhang J.; Xue Y.; Zhang Y.; Penicamedine A, a highly oxy-genated hexacyclic indole alkaloid from Penicillium camemberti. Chem Biodivers 2015,12(10),1547-1553 Bioorg Med Chem Lett Ding L. 20 6685 2010 10.1016/j.bmcl.2010.09.010 Ding L.; Münch J.; Goerls H.; Maier A.; Fiebig H.H.; Lin W.H.; Hertweck C.; Xiamycin, a pentacyclic indolosesquiterpene with selec-tive anti-HIV activity from a bacterial mangrove endophyte. Bioorg Med Chem Lett 2010,20(22),6685-6687 Acc Chem Res Meunier B. 41 69 2008 10.1021/ar7000843 Meunier B.; Hybrid molecules with a dual mode of action: dream or reality? Acc Chem Res 2008,41(1),69-77 Eur J Med Chem 124 500 2016 10.1016/j.ejmech.2016.08.039 Shaveta; Mishra, S.; Singh, P. Hybrid molecules: The privileged scaffolds for various pharmaceuticals. Eur J Med Chem 2016,124,500-536 Eur J Med Chem Gu S.X. 174 277 2019 10.1016/j.ejmech.2019.04.054 Gu S.X.; Xiao T.; Zhu Y.Y.; Liu G.Y.; Chen F.E.; Recent progress in HIV-1 inhibitors targeting the entrance channel of HIV-1 non-nucleoside reverse transcriptase inhibitor binding pocket. Eur J Med Chem 2019,174,277-291 ChemMedChem Shirvani P. 14 52 2019 10.1002/cmdc.201800577 Shirvani P.; Fassihi A.; Saghaie L.; Recent advances in the design and development of nonnucleoside reverse transcriptase inhibitor scaffolds. ChemMedChem 2019,14(1),52-77 Mini Rev Med Chem Ölgen S. 13 1700 2013 10.2174/13895575113139990075 Ölgen S.; Recent development of new substituted indole and azaindole derivatives as anti-HIV agents. Mini Rev Med Chem 2013,13(12),1700-1708 Future Med Chem Famiglini V. 5 2141 2013 10.4155/fmc.13.174 Famiglini V.; Coluccia A.; Brancale A.; Pelliccia S.; La Regina G.; Silvestri R.; Arylsulfone-based HIV-1 non-nucleoside reverse tran-scriptase inhibitors. Future Med Chem 2013,5(18),2141-2156 Eur J Med Chem Famiglini V. 80 101 2014 10.1016/j.ejmech.2014.04.027 Famiglini V.; La Regina G.; Coluccia A.; Pelliccia S.; Brancale A.; Maga G.; Crespan E.; Badia R.; Clotet B.; Esté J.A.; Cirilli R.; Novellino E.; Silvestri R.; New indolylarylsulfones as highly potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase in-hibitors. Eur J Med Chem 2014,80,101-111 Tetrahedron Lett Tocco G. 54 6237 2013 10.1016/j.tetlet.2013.09.017 Tocco G.; Begala M.; Esposito F.; Caboni P.; Cannas V.; Tramontano E.; ZnO-mediated regioselective C-arylsulfonylation of indoles: A facile solvent-free synthesis of 2- and 3-sulfonylindoles and preliminary evaluation of their activity against drug-resistant mutant HIV-1 reverse transcriptases (RTs). Tetrahedron Lett 2013,54,6237-6241 Pharmaceuticals (Basel) Che Z. 8 221 2015 10.3390/ph8020221 Che Z.; Liu S.; Tian Y.; Hu Z.; Chen Y.; Chen G.; Design and synthesis of novel N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives as inhibitors of HIV-1 replication. Pharmaceuticals (Basel) 2015,8(2),221-229 J Med Chem La Regina G. 54 1587 2011 10.1021/jm101614j La Regina G.; Coluccia A.; Brancale A.; Piscitelli F.; Gatti V.; Maga G.; Samuele A.; Pannecouque C.; Schols D.; Balzarini J.; No-vellino E.; Silvestri R.; Indolylarylsulfones as HIV-1 non-nucleoside reverse transcriptase inhibitors: new cyclic substituents at indole-2-carboxamide. J Med Chem 2011,54(6),1587-1598 J Med Chem La Regina G. 55 6634 2012 10.1021/jm300477h La Regina G.; Coluccia A.; Brancale A.; Piscitelli F.; Famiglini V.; Cosconati S.; Maga G.; Samuele A.; Gonzalez E.; Clotet B.; Schols D.; Esté J.A.; Novellino E.; Silvestri R.; New nitrogen containing substituents at the indole-2-carboxamide yield high potent and broad spectrum indolylarylsulfone HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem 2012,55(14),6634-6638 J Med Chem Famiglini V. 57 9945 2014 10.1021/jm5011622 Famiglini V.; La Regina G.; Coluccia A.; Pelliccia S.; Brancale A.; Maga G.; Crespan E.; Badia R.; Riveira-Muñoz E.; Esté J.A.; Ferretti R.; Cirilli R.; Zamperini C.; Botta M.; Schols D.; Limongelli V.; Agostino B.; Novellino E.; Silvestri R.; Indolylarylsulfones carrying a heterocyclic tail as very potent and broad spectrum HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem 2014,57(23),9945-9957 J Mol Graph Model Massarotti A. 63 49 2016 10.1016/j.jmgm.2015.11.013 Massarotti A.; Coluccia A.; An in-silico approach aimed to clarify the role of Y181C and K103N HIV-1 reverse transcriptase mutations versus Indole Aryl Sulphones. J Mol Graph Model 2016,63,49-56 J Med Chem Famiglini V. 60 6528 2017 10.1021/acs.jmedchem.6b01906 Famiglini V.; La Regina G.; Coluccia A.; Masci D.; Brancale A.; Badia R.; Riveira-Muñoz E.; Esté J.A.; Crespan E.; Brambilla A.; Maga G.; Catalano M.; Limatola C.; Formica F.R.; Cirilli R.; Novellino E.; Silvestri R.; Chiral indolylarylsulfone non-nucleoside re-verse transcriptase inhibitors as new potent and broad-spectrum anti-HIV-1 agents. J Med Chem 2017,60(15),6528-6547 Eur J Med Chem Li X. 126 190 2017 10.1016/j.ejmech.2016.10.009 Li X.; Gao P.; Huang B.; Zhou Z.; Yu Z.; Yuan Z.; Liu H.; Pannecouque C.; Daelemans D.; De Clercq E.; Zhan P.; Liu X.; Discov-ery of novel piperidine-substituted indolylarylsulfones as potent HIV NNRTIs via structure-guided scaffold morphing and fragment re-arrangement. Eur J Med Chem 2017,126,190-201 Farmacia Ravichandran V. 64 745 2016 Ravichandran V.; Shalini S.; Venkateskumar K.; Dhanaraj S.A.; Exploring the structural insights of indole-7-carboxamides as anti-HIV agents. Farmacia 2016,64,745-756 Eur J Med Chem Zhao T. 182 111619 2019 10.1016/j.ejmech.2019.111619 Zhao T.; Meng Q.; Kang D.; Ji J.; De Clercq E.; Pannecouque C.; Liu X.; Zhan P.; Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing. Eur J Med Chem 2019,182,111619 Mini Rev Med Chem Das R. 16 290 2019 10.2174/1570193X15666180622144414 Das R.; Asthana G.S.; Suri K.A.; Mehta D.; Asthana A.; Recent developments in azole compounds as antitubercular agent. Mini Rev Med Chem 2019,16,290-306 Mini Rev Med Chem Zhang H.Z. 17 122 2017 10.2174/1389557516666160630120725 Zhang H.Z.; Gan L.L.; Wang H.; Zhou C.H.; New progress in azole compounds as antimicrobial agents. Mini Rev Med Chem 2017,17(2),122-166 Int J Pharm Sci Res Singh R. 8 29 2017 Singh R.; Gupta S.; Singh J.; Arsi T.; Azoles as non-nucleoside reverse transcriptase inhibitors (NNRTIS): Mini review. Int J Pharm Sci Res 2017,8,29-34 Curr Pharm Des de Oliveira Viana J. 25 4702 2019 10.2174/1381612825666191125090700 de Oliveira Viana J.; Monteiro A.F.M.; Filho J.M.B.; Scotti L.; Scotti M.T.; The azoles in pharmacochemistry: Perspectives on the synthesis of new compounds and chemoinformatic contributions. Curr Pharm Des 2019,25(44),4702-4716 Med Chem Singh I.P. 16 4 2020 10.2174/1573406415666190614101253 Singh I.P.; Gupta S.; Kumar S.; Thiazole compounds as antiviral agents: An update. Med Chem 2020,16(1),4-23 Expert Opin Drug Discov Gao P. 11 857 2016 10.1080/17460441.2016.1210125 Gao P.; Sun L.; Zhou J.; Li X.; Zhan P.; Liu X.; Discovery of novel anti-HIV agents via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry-based approach. Expert Opin Drug Discov 2016,11(9),857-871 Bioorg Med Chem Lett Yeung K.S. 23 198 2013 10.1016/j.bmcl.2012.10.115 Yeung K.S.; Qiu Z.; Xue Q.; Fang H.; Yang Z.; Zadjura L.; D’Arienzo C.J.; Eggers B.J.; Riccardi K.; Shi P.Y.; Gong Y.F.; Brown-ing M.R.; Gao Q.; Hansel S.; Santone K.; Lin P.F.; Meanwell N.A.; Kadow J.F.; Inhibitors of HIV-1 attachment. Part 7: indole-7-carboxamides as potent and orally bioavailable antiviral agents. Bioorg Med Chem Lett 2013,23(1),198-202 Bioorg Med Chem Lett Yeung K.S. 23 203 2013 10.1016/j.bmcl.2012.10.117 Yeung K.S.; Qiu Z.; Yin Z.; Trehan A.; Fang H.; Pearce B.; Yang Z.; Zadjura L.; D’Arienzo C.J.; Riccardi K.; Shi P.Y.; Spicer T.P.; Gong Y.F.; Browning M.R.; Hansel S.; Santone K.; Barker J.; Coulter T.; Lin P.F.; Meanwell N.A.; Kadow J.F.; Inhibitors of HIV-1 attachment. Part 8: the effect of C7-heteroaryl substitution on the potency, and in vitro and in vivo profiles of indole-based inhibi-tors. Bioorg Med Chem Lett 2013,23(1),203-208 Bioorg Med Chem Lett Yeung K.S. 23 209 2013 10.1016/j.bmcl.2012.10.125 Yeung K.S.; Qiu Z.; Yang Z.; Zadjura L.; D’Arienzo C.J.; Browning M.R.; Hansel S.; Huang X.S.; Eggers B.J.; Riccardi K.; Lin P.F.; Meanwell N.A.; Kadow J.F.; Inhibitors of HIV-1 attachment. Part 9: an assessment of oral prodrug approaches to improve the plasma exposure of a tetrazole-containing derivative. Bioorg Med Chem Lett 2013,23(1),209-212 RSC Advances Wang J. 5 78278 2015 10.1039/C5RA04299B Wang J.; Li Y.; Yang Y.; Zhang J.; Du J.; Zhang S.; Yang L.; Profiling the interaction mechanism of indolebased derivatives targeting the HIV-1 gp120 receptor. RSC Advances 2015,5,78278-78298 Eur J Med Chem Meleddu R. 93 452 2015 10.1016/j.ejmech.2015.02.032 Meleddu R.; Distinto S.; Corona A.; Bianco G.; Cannas V.; Esposito F.; Artese A.; Alcaro S.; Matyus P.; Bogdan D.; Cottiglia F.; Tramontano E.; Maccioni E.; (3Z)-3-(2-[4-(aryl)-1, 3-thiazol-2-yl]hydrazin-1-ylidene)-2, 3-dihydro-1H-indol-2-one derivatives as dual inhibitors of HIV-1 reverse transcriptase. Eur J Med Chem 2015,93,452-460 J Enzyme Inhib Med Chem Meleddu R. 32 130 2017 10.1080/14756366.2016.1238366 Meleddu R.; Distinto S.; Corona A.; Tramontano E.; Bianco G.; Melis C.; Cottiglia F.; Maccioni E.; Isatin thiazoline hybrids as dual inhibitors of HIV-1 reverse transcriptase. J Enzyme Inhib Med Chem 2017,32(1),130-136 Med Chem Res Pawar V.S. 20 370 2011 10.1007/s00044-010-9329-y Pawar V.S.; Lokwani D.K.; Bhandari S.V.; Bothara K.G.; Chitre T.S.; Devale T.L.; Modhave N.S.; Parikh J.K.; Design, docking study and ADME prediction of isatin derivatives as anti-HIV agents. Med Chem Res 2011,20,370-380 PLoS One Corona A. 11 e0147225 2016 10.1371/journal.pone.0147225 Corona A.; Meleddu R.; Esposito F.; Distinto S.; Bianco G.; Masaoka T.; Maccioni E.; Menéndez-Arias L.; Alcaro S.; Le Grice S.F.; Tramontano E.; Ribonuclease H/DNA polymerase HIV-1 reverse transcriptase dual inhibitor: Mechanistic studies on the allosteric mode of action of isatin-based compound RMNC6. PLoS One 2016,11(1),e0147225 Eur J Med Chem Liu T. 86 481 2014 10.1016/j.ejmech.2014.09.012 Liu T.; Huang B.; Zhan P.; De Clercq E.; Liu X.; Discovery of small molecular inhibitors targeting HIV-1 gp120-CD4 interaction drived from BMS-378806. Eur J Med Chem 2014,86,481-490 J Med Chem Meanwell N.A. 61 62 2018 10.1021/acs.jmedchem.7b01337 Meanwell N.A.; Krystal M.R.; Nowicka-Sans B.; Langley D.R.; Conlon D.A.; Eastgate M.D.; Grasela D.M.; Timmins P.; Wang T.; Kadow J.F.; Inhibitors of HIV-1 attachment: The discovery and development of temsavir and its prodrug fostemsavir. J Med Chem 2018,61(1),62-80 J Med Chem Regueiro-Ren A. 56 1656 2013 10.1021/jm3016377 Regueiro-Ren A.; Xue Q.M.; Swidorski J.J.; Gong Y.F.; Mathew M.; Parker D.D.; Yang Z.; Eggers B.; D’Arienzo C.; Sun Y.; Mali-nowski J.; Gao Q.; Wu D.; Langley D.R.; Colonno R.J.; Chien C.; Grasela D.M.; Zheng M.; Lin P.F.; Meanwell N.A.; Kadow J.F.; Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 12. Structure-activity relationships associated with 4-fluoro-6-azaindole derivatives leading to the identification of 1-(4-benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1, 2, 3]triazol-1-yl-1h-pyrrolo[2, 3-c]pyridin-3-yl)ethane-1, 2-dione (BMS-585248). J Med Chem 2013,56(4),1656-1669 J Med Chem Wang T. 61 6308 2018 10.1021/acs.jmedchem.8b00759 Wang T.; Ueda Y.; Zhang Z.; Yin Z.; Matiskella J.; Pearce B.C.; Yang Z.; Zheng M.; Parker D.D.; Yamanaka G.A.; Gong Y.F.; Ho H.T.; Colonno R.J.; Langley D.R.; Lin P.F.; Meanwell N.A.; Kadow J.F.; Discovery of the human immunodeficiency virus type 1 (HIV-1) attachment inhibitor temsavir and its phosphonooxymethyl prodrug fostemsavir. J Med Chem 2018,61(14),6308-6327 Arch Pharm Res Balupuri A. 37 1001 2014 10.1007/s12272-013-0313-1 Balupuri A.; Gadhe C.G.; Balasubramanian P.K.; Kothandan G.; Cho S.J.; In silico study on indole derivatives as anti HIV-1 agents: a combined docking, molecular dynamics and 3D-QSAR study. Arch Pharm Res 2014,37(8),1001-1015 J Med Chem Kadow J.F. 55 2048 2012 10.1021/jm201218m Kadow J.F.; Ueda Y.; Meanwell N.A.; Connolly T.P.; Wang T.; Chen C.P.; Yeung K.S.; Zhu J.; Bender J.A.; Yang Z.; Parker D.; Lin P.F.; Colonno R.J.; Mathew M.; Morgan D.; Zheng M.; Chien C.; Grasela D.; Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment 6. Preclinical and human pharmacokinetic profiling of BMS-663749, a phosphonooxymethyl prodrug of the HIV-1 attachment inhibitor 2-(4-benzoyl-1-piperazinyl)-1-(4, 7-dimethoxy-1H-pyrrolo[2, 3-c]pyridin-3-yl)-2-oxoethanone (BMS-488043). J Med Chem 2012,55(5),2048-2056 Bioorg Med Chem Lett Wang T. 29 1423 2019 10.1016/j.bmcl.2019.03.018 Wang T.; Wallace O.B.; Zhang Z.; Fang H.; Yang Z.; Robinson B.A.; Spicer T.P.; Gong Y.F.; Blair W.S.; Shi P.Y.; Lin P.F.; Desh-pande M.; Meanwell N.A.; Kadow J.F.; A survey of core replacements in indole-based HIV-1 attachment inhibitors. Bioorg Med Chem Lett 2019,29(11),1423-1429 Molecules Karadsheh R. 25 e1430 2020 10.3390/molecules25061430 Karadsheh R.; Meuser M.E.; Cocklin S.; Composition and orientation of the core region of novel HIV-1 entry inhibitors influences metabolic stability. Molecules 2020,25(6),e1430 Curr Drug Metab Xu F. 18 769 2017 10.2174/1389200218666170724112412 Xu F.; Acosta E.P.; Liang L.; He Y.; Yang J.; Kerstner-Wood C.; Zheng Q.; Huang J.; Wang K.; Wang K.; Current status of the pharmacokinetics and pharmacodynamics of HIV-1 entry inhibitors and HIV therapy. Curr Drug Metab 2017,18(8),769-781 Proteins Langley D.R. 83 331 2015 10.1002/prot.24726 Langley D.R.; Kimura S.R.; Sivaprakasam P.; Zhou N.; Dicker I.; McAuliffe B.; Wang T.; Kadow J.F.; Meanwell N.A.; Krystal M.; Homology models of the HIV-1 attachment inhibitor BMS-626529 bound to gp120 suggest a unique mechanism of action. Proteins 2015,83(2),331-350 Antimicrob Agents Chemother Li Z. 57 4172 2013 10.1128/AAC.00513-13 Li Z.; Zhou N.; Sun Y.; Ray N.; Lataillade M.; Hanna G.J.; Krystal M.; Activity of the HIV-1 attachment inhibitor BMS-626529, the active component of the prodrug BMS-663068, against CD4-independent viruses and HIV-1 envelopes resistant to other entry inhibi-tors. Antimicrob Agents Chemother 2013,57(9),4172-4180 J Infect Dis Nettles R.E. 206 1002 2012 10.1093/infdis/jis432 Nettles R.E.; Schürmann D.; Zhu L.; Stonier M.; Huang S.P.; Chang I.; Chien C.; Krystal M.; Wind-Rotolo M.; Ray N.; Hanna G.J.; Bertz R.; Grasela D.; Pharmacodynamics, safety, and pharmacokinetics of BMS-663068, an oral HIV-1 attachment inhibitor in HIV-1-infected subjects. J Infect Dis 2012,206(7),1002-1011 Clin Transl Sci Lagishetty C. 13 769 2020 10.1111/cts.12763 Lagishetty C.; Moore K.; Ackerman P.; Llamoso C.; Magee M.; Effects of temsavir, active moiety of antiretroviral agent fostemsavir, on QT interval: Results from a phase I study and an exposure-response analysis. Clin Transl Sci 2020,13(4),769-776 J Med Chem Li D. 55 3595 2012 10.1021/jm200990c Li D.; Zhan P.; De Clercq E.; Liu X.; Strategies for the design of HIV-1 non-nucleoside reverse transcriptase inhibitors: lessons from the development of seven representative paradigms. J Med Chem 2012,55(8),3595-3613 Chem Res Toxicol Castellino S. 26 241 2013 10.1021/tx3004196 Castellino S.; Groseclose M.R.; Sigafoos J.; Wagner D.; de Serres M.; Polli J.W.; Romach E.; Myer J.; Hamilton B.; Central nervous system disposition and metabolism of Fosdevirine (GSK2248761), a non-nucleoside reverse transcriptase inhibitor: an LC-MS and Ma-trix-assisted laser desorption/ionization imaging MS investigation into central nervous system toxicity. Chem Res Toxicol 2013,26(2),241-251 Br J Clin Pharmacol Piscitelli S. 74 336 2012 10.1111/j.1365-2125.2012.04194.x Piscitelli S.; Kim J.; Gould E.; Lou Y.; White S.; de Serres M.; Johnson M.; Zhou X.J.; Pietropaolo K.; Mayers D.; Drug interaction profile for GSK2248761, a next generation non-nucleoside reverse transcriptase inhibitor. Br J Clin Pharmacol 2012,74(2),336-345 Antimicrob Agents Chemother Zala C. 56 2570 2012 10.1128/AAC.05597-11 Zala C.; St Clair M.; Dudas K.; Kim J.; Lou Y.; White S.; Piscitelli S.; Dumont E.; Pietropaolo K.; Zhou X.J.; Mayers D.; Safety and efficacy of GSK2248761, a next-generation nonnucleoside reverse transcriptase inhibitor, in treatment-naive HIV-1-infected subjects. Antimicrob Agents Chemother 2012,56(5),2570-2575 Antivir Ther Margolis D.A. 19 69 2014 10.3851/IMP2689 Margolis D.A.; Eron J.J.; DeJesus E.; White S.; Wannamaker P.; Stancil B.; Johnson M.; Unexpected finding of delayed-onset sei-zures in HIV-positive, treatment-experienced subjects in the Phase IIb evaluation of fosdevirine (GSK2248761). Antivir Ther 2014,19(1),69-78 J Med Chem Alexandre F.R. 54 392 2011 10.1021/jm101142k Alexandre F.R.; Amador A.; Bot S.; Caillet C.; Convard T.; Jakubik J.; Musiu C.; Poddesu B.; Vargiu L.; Liuzzi M.; Roland A.; Seifer M.; Standring D.; Storer R.; Dousson C.B.; Synthesis and biological evaluation of aryl-phospho-indole as novel HIV-1 non-nucleoside reverse transcriptase inhibitors. J Med Chem 2011,54(1),392-395 J Med Chem Dousson C. 59 1891 2016 10.1021/acs.jmedchem.5b01430 Dousson C.; Alexandre F.R.; Amador A.; Bonaric S.; Bot S.; Caillet C.; Convard T.; da Costa D.; Lioure M.P.; Roland A.; Rosi-novsky E.; Maldonado S.; Parsy C.; Trochet C.; Storer R.; Stewart A.; Wang J.; Mayes B.A.; Musiu C.; Poddesu B.; Vargiu L.; Liuzzi M.; Moussa A.; Jakubik J.; Hubbard L.; Seifer M.; Standring D.; Discovery of the aryl-phospho-indole IDX899, a highly po-tent anti-HIV non-nucleoside reverse transcriptase inhibitor. J Med Chem 2016,59(5),1891-1898 Phytochem Rev Ibrahim S.R.M. 15 197 2016 10.1007/s11101-015-9403-7 Ibrahim S.R.M.; Abdallah H.M.; El-Halawany A.M.; Mohamed G.A.; Naturally occurring thiophenes: Isolation, purification, structural elucidation, and evaluation of bioactivities. Phytochem Rev 2016,15,197-220 Expert Opin Investig Drugs D’Cruz O.J. 21 265 2012 10.1517/13543784.2012.655422 D’Cruz O.J.; Qazi S.; Yiv S.; Uckun F.M.; A novel vaginal microbicide containing the rationally designed anti-HIV compound HI-443 (N-[2-(2-thiophene)ethyl]-N-[2-(5-bromopyridyl)] thiourea]). Expert Opin Investig Drugs 2012,21(3),265-279 Med Chem Res Gadhe C.G. 21 1892 2012 10.1007/s00044-011-9711-4 Gadhe C.G.; Kothandan G.; Madhavan T.; Cho S.J.; Molecular modeling study of HIV-1 gp120 attachment inhibitors. Med Chem Res 2012,21,1892-1904 Antiinfect Agents Patel B.D. 15 115 2017 Patel B.D.; Choksi N.; Patel K.; Gulamnizami Q.; D-QSAR and molecular docking studies of HIV-1 entry inhibitors targeting GP120-CD4 binding site. Antiinfect Agents 2017,15,115-130 ACS Med Chem Lett Hassam M. 3 470 2012 10.1021/ml3000462 Hassam M.; Basson A.E.; Liotta D.C.; Morris L.; van Otterlo W.A.L.; Pelly S.C.; Novel cyclopropyl-indole derivatives as HIV non-nucleoside reverse transcriptase inhibitors. ACS Med Chem Lett 2012,3(6),470-475 Bioorg Chem El-Hussieny M. 95 103521 2020 10.1016/j.bioorg.2019.103521 El-Hussieny M.; El-Sayed N.F.; Ewies E.F.; Ibrahim N.M.; Mahran M.R.H.; Fouad M.A.; Synthesis, molecular docking and biological evaluation of 2-(thiophen-2-yl)-1H-indoles as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Bioorg Chem 2020,95,103521 Bioorg Med Chem Lett Wang T. 23 213 2013 10.1016/j.bmcl.2012.10.120 Wang T.; Yang Z.; Zhang Z.; Gong Y.F.; Riccardi K.A.; Lin P.F.; Parker D.D.; Rahematpura S.; Mathew M.; Zheng M.; Meanwell N.A.; Kadow J.F.; Bender J.A.; Inhibitors of HIV-1 attachment. Part 10. The discovery and structure-activity relationships of 4-azaindole cores. Bioorg Med Chem Lett 2013,23(1),213-217 Chem Biol Drug Des Ashok P. 85 722 2015 10.1111/cbdd.12456 Ashok P.; Lu C.L.; Chander S.; Zheng Y.T.; Murugesan S.; Design, synthesis, and biological evaluation of 1-(thiophen-2-yl)-9H-pyrido[3, 4-b]indole derivatives as anti-HIV-1 agents. Chem Biol Drug Des 2015,85(6),722-728 Med Chem Res Penta A. 23 3662 2014 10.1007/s00044-014-0945-9 Penta A.; Chander S.; Ganguly S.; Murugesan S.; De novo design and in-silico studies of novel 1-phenyl-2, 3, 4, 9-tetrahydro-1H-pyrido[3, 4-b]indole-3-carboxylic acid derivatives as HIV-1 reverse transcriptase inhibitors. Med Chem Res 2014,23,3662-3670 Pharma Chem El-Shorbagi A.A. 7 87 2015 El-Shorbagi A.A.; Abdel-Moty S.G.; Ahmed A.N.; Takayama H.; Kitajima M.; Aimi N.; Sakai S.; The antiviral (RNA & DNA) profile of some incomplete C-nucleosides inspired from natural -carboline (pyrido[3, 4-b]indole) scaffold; pharmacology of the intermediates in the total synthesis. Pharma Chem 2015,7,87-92 Eur J Med Chem Xu C. 189 112071 2020 10.1016/j.ejmech.2020.112071 Xu C.; Xin Y.; Chen M.; Ba M.; Guo Q.; Zhu C.; Guo Y.; Shi J.; Discovery, synthesis, and optimization of an N-alkoxy indolyla-cetamide against HIV-1 carrying NNRTI-resistant mutations from the Isatis indigotica root. Eur J Med Chem 2020,189,112071 Bioorg Chem Devale T.L. 70 256 2017 10.1016/j.bioorg.2017.01.006 Devale T.L.; Parikh J.; Miniyar P.; Sharma P.; Shrivastava B.; Murumkar P.; Dihydropyrimidinone-isatin hybrids as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. Bioorg Chem 2017,70,256-266 Bioorg Med Chem Pawar V. 18 3198 2010 10.1016/j.bmc.2010.03.030 Pawar V.; Lokwani D.; Bhandari S.; Mitra D.; Sabde S.; Bothara K.; Madgulkar A.; Design of potential reverse transcriptase inhibitor containing Isatin nucleus using molecular modeling studies. Bioorg Med Chem 2010,18(9),3198-3211 Eur J Med Chem Banerjee D. 46 106 2011 10.1016/j.ejmech.2010.10.020 Banerjee D.; Yogeeswari P.; Bhat P.; Thomas A.; Srividya M.; Sriram D.; Novel isatinyl thiosemicarbazones derivatives as potential molecule to combat HIV-TB co-infection. Eur J Med Chem 2011,46(1),106-121 Med Chem Res Upadhyay K. 22 3675 2013 10.1007/s00044-012-0342-1 Upadhyay K.; Manvar A.; Loddo R.; Colla P.L.; Virsodiya V.; Trivedi J.; Chaniyara R.; Shah A.; Syntheses and in vitro biological screening of 1-aryl-10H-[1, 2, 4]triazolo[3 43, 4][1, 2, 4]triazino[5, 6-b]indoles. Med Chem Res 2013,22,3675-3686 Bioorg Med Chem Lett Patel P.A. 26 4748 2016 10.1016/j.bmcl.2016.08.037 Patel P.A.; Kvaratskhelia N.; Mansour Y.; Antwi J.; Feng L.; Koneru P.; Kobe M.J.; Jena N.; Shi G.; Mohamed M.S.; Li C.; Kessl J.J.; Fuchs J.R.; Indole-based allosteric inhibitors of HIV-1 integrase. Bioorg Med Chem Lett 2016,26(19),4748-4752 Synlett Kasralikar H.M. 26 1969 2015 10.1055/s-0034-1381043 Kasralikar H.M.; Jadhavar S.C.; Bhusare S.R.; Synthesis and molecular docking study of novel chromenochromenones as anti-HIV-1 NNRT Inhibitors. Synlett 2015,26,1969-1972 Med Chem Wang J. 10 738 2014 10.2174/1573406410666140306151815 Wang J.; Wang Y.; Li Z.; Zhan P.; Bai R.; Pannecouque C.; Balzarini J.; De Clercq E.; Liu X.; Design, synthesis and biological evalu-ation of substituted guanidine indole derivatives as potential inhibitors of HIV-1 Tat-TAR interaction. Med Chem 2014,10(7),738-746 Bioorg Med Chem Lett Kasralikar H.M. 25 3882 2015 10.1016/j.bmcl.2015.07.050 Kasralikar H.M.; Jadhavar S.C.; Bhusare S.R.; Synthesis and molecular docking studies of oxochromenyl xanthenone and indolyl xan-thenone derivatives as anti-HIV-1 RT inhibitors. Bioorg Med Chem Lett 2015,25(18),3882-3886 Org Biomol Chem Liang G. 14 7875 2016 10.1039/C6OB01334A Liang G.; Wang H.; Chong H.; Cheng S.; Jiang X.; He Y.; Wang C.; Liu K.; An effective conjugation strategy for designing short pep-tide-based HIV-1 fusion inhibitors. Org Biomol Chem 2016,14(33),7875-7882 MedChemComm Yang Q. 8 1806 2017 10.1039/C7MD00327G Yang Q.; Ding Y.; Feng F.; Pan E.; Fan X.; Ma X.; Chen L.; Zhao J.; Sun C.; Structure-optimized dihydropyranoindole derivative GIBH-LRA002 potentially reactivated viral latency in primary CD4+ T lymphocytes of chronic HIV-1 patients. MedChemComm 2017,8(9),1806-1809 Molecules Sanna G. 23 e2554 2018 10.3390/molecules23102554 Sanna G.; Madeddu S.; Giliberti G.; Piras S.; Struga M.; Wrzosek M.; Kubiak-Tomaszewska G.; Koziol A.E.; Savchenko O.; Lis T.; Stefanska J.; Tomaszewski P.; Skrzycki M.; Szulczyk D.; SAvchenko, O.; Lis, T.; Stefanska, J.; Tomaszewski, P.; Skrzycki, M.; Szulczyk, D. Synthesis and biological evaluation of novel indole-derived thioureas. Molecules 2018,23(10),e2554 ChemPlusChem Martin C. 85 207 2020 10.1002/cplu.201900650 Martin C.; Piccoli S.D.; Gaysinski M.; Becquart C.; Azoulay S.; Giorgio A.D.; Duca M.; Unveiling RNA-binding properties of vera-pamil and preparation of new derivatives as inhibitors of HIV-1 Tat-TAR interaction. ChemPlusChem 2020,85,207-216 Arch Pharm Yang P. 57 526 2020 Yang P.; Lu M.; Li K.; Xie Y.; Artemisinin-derived dimers and their antimalarial activities. Arch Pharm 2020,57,526-534 Curr Top Med Chem Ren Q.C. 18 101 2018 10.2174/1568026618666180221114515 Ren Q.C.; Gao C.; Xu Z.; Feng L.S.; Liu M.L.; Wu X.; Zhao F.; Bis-coumarin derivatives and their biological activities. Curr Top Med Chem 2018,18(2),101-113 Eur J Med Chem Zhou G. 161 533 2019 10.1016/j.ejmech.2018.10.048 Zhou G.; Chu S.; Nemati A.; Huang C.; Snyder B.A.; Ptak R.G.; Gochin M.; Investigation of the molecular characteristics of bisindole inhibitors as HIV-1 glycoprotein-41 fusion inhibitors. Eur J Med Chem 2019,161,533-542 J Med Chem Zhou G. 54 7220 2011 10.1021/jm200791z Zhou G.; Wu D.; Snyder B.; Ptak R.G.; Kaur H.; Gochin M.; Development of indole compounds as small molecule fusion inhibitors targeting HIV-1 glycoprotein-41. J Med Chem 2011,54(20),7220-7231 J Med Chem Zhou G. 57 5270 2014 10.1021/jm500344y Zhou G.; Sofiyev V.; Kaur H.; Snyder B.A.; Mankowski M.K.; Hogan P.A.; Ptak R.G.; Gochin M.; Structure-activity relationship studies of indole-based compounds as small molecule HIV-1 fusion inhibitors targeting glycoprotein 41. J Med Chem 2014,57(12),5270-5281 J Med Chem Martínez-Gualda B. 63 349 2020 10.1021/acs.jmedchem.9b01737 Martínez-Gualda B.; Sun L.; Martí-Marí O.; Noppen S.; Abdelnabi R.; Bator C.M.; Quesada E.; Delang L.; Mirabelli C.; Lee H.; Schols D.; Neyts J.; Hafenstein S.; Camarasa M.J.; Gago F.; San-Félix A.; Scaffold simplification strategy leads to a novel generation of dual human immunodeficiency virus and enterovirus-A71 entry inhibitors. J Med Chem 2020,63(1),349-368

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