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Current Cancer Therapy Reviews

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ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

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Review Article

A Review on Indole as a Cardinal Scaffold for Anticancer Drugs Development

Author(s): Meenakshi Rana, Rajeev Ranjan, Niladry Sekhar Ghosh, Dharmendra Kumar* and Ranjit Singh

Volume 20, Issue 4, 2024

Published on: 10 October, 2023

Page: [372 - 385] Pages: 14

DOI: 10.2174/0115733947249518231001001728

Price: $65

Abstract

Chemotherapy is the mainstay of therapeutic cancer therapy; however, the development of resistance typically makes it less effective. There are continuous efforts by researchers to find novel lead compounds with potent anti-cancer activity. Generally, synthetic or natural heterocyclic compounds have been investigated in detail as a scaffold for cancer therapeutics. Among them, indole, owing to its unique physiochemical and biological properties, provides a promising platform for the development of pharmacophores for drug development against cancer, acting via various mechanisms. Till now, several indole-based derivatives have been identified as anti-cancer agents, which are either being used in clinics or are in various phases of clinical trials, suggesting their importance in anti-cancer drug development. These anti-cancer drugs have been classified into different classes depending on their mechanism of action. For example, histone deacetylase inhibitors (HDAC inhibitors), silent mating type information regulation 2 homolog (SIRT) inhibitors, tubulin inhibitors, proviral insertion site in Moloney murine leukemia virus (Pim) inhibitors, DNA Topoisomerase inhibitors, and kinase inhibitors. In this review, the author's approach is to compile the recent developments on indole-based anti-cancer drugs and provide insight into the respective structureactivity relationships (SARs) of the compounds. We hope the review will provide a thorough understanding to the reader and guide to developing novel and potent indole-based anticancer agents against drug-sensitive and drug-resistant cancer in the future.

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[1]
Ferlay J, Ervik M, Lam F, et al. Global Cancer Observatory: Cancer Today. Lyon: International Agency for Research on Cancer 2020.
[2]
World Cancer Research Fund International. Worldwide cancer data. 2023. Available From: https://www.wcrf.org/cancer-trends/world wide-cancer-data/
[3]
Zhang H, Yang F, Chen SJ, Che J, Zheng J. Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol 2015; 36(4): 2947-55.
[http://dx.doi.org/10.1007/s13277-014-2925-6] [PMID: 25480417]
[4]
Mansoori B, Mohammadi A, Davudian S, Shirjang S, Baradaran B. The different mechanisms of cancer drug resistance: A brief review. Adv Pharm Bull 2017; 7(3): 339-48.
[http://dx.doi.org/10.15171/apb.2017.041] [PMID: 29071215]
[5]
Cardoso D, Szemerédi N, Spengler G, Mulhovo S, dos Santos D, Ferreira MJ. Exploring the monoterpene indole alkaloid scaffold for reversing P-glycoprotein-mediated multidrug resistance in cancer. Pharmaceuticals (Basel) 2021; 14(9): 862.
[http://dx.doi.org/10.3390/ph14090862] [PMID: 34577562]
[6]
Sidhu JS, Singla R, Mayank , Jaitak V. Indole derivatives as anticancer agents for breast cancer therapy: A review. Anticancer Agents Med Chem 2015; 16(2): 160-73.
[http://dx.doi.org/10.2174/1871520615666150520144217] [PMID: 25991424]
[7]
Xu D, Xu Z. Indole alkaloids with potential anticancer activity. Curr Top Med Chem 2020; 20(21): 1938-49.
[http://dx.doi.org/10.2174/1568026620666200622150325] [PMID: 32568021]
[8]
Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 2006; 6(1): 38-51.
[http://dx.doi.org/10.1038/nrc1779] [PMID: 16397526]
[9]
Gregoretti I, Lee YM, Goodson HV. Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J Mol Biol 2004; 338(1): 17-31.
[http://dx.doi.org/10.1016/j.jmb.2004.02.006] [PMID: 15050820]
[10]
Chen X, Zhao S, Li H, et al. Design, synthesis and biological evaluation of novel isoindolinone derivatives as potent histone deacetylase inhibitors. Eur J Med Chem 2019; 168: 110-22.
[http://dx.doi.org/10.1016/j.ejmech.2019.02.032] [PMID: 30802729]
[11]
Kalin JH, Bergman JA. Development and therapeutic implications of selective histone deacetylase 6 inhibitors. J Med Chem 2013; 56(16): 6297-313.
[http://dx.doi.org/10.1021/jm4001659] [PMID: 23627282]
[12]
Lourenço de Freitas N, Deberaldini MG, Gomes D, et al. Histone deacetylase inhibitors as therapeutic interventions on cervical cancer induced by human papillomavirus. Front Cell Dev Biol 2021; 8: 592868.
[http://dx.doi.org/10.3389/fcell.2020.592868] [PMID: 33634093]
[13]
Sangwan R, Rajan R, Mandal PK. HDAC as onco target: Reviewing the synthetic approaches with SAR study of their inhibitors. Eur J Med Chem 2018; 158: 620-706.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.073] [PMID: 30245394]
[14]
Laubach JP, Moreau P, San-Miguel JF, Richardson PG. Panobinostat for the Treatment of Multiple Myeloma. Clin Cancer Res 2015; 21(21): 4767-73.
[http://dx.doi.org/10.1158/1078-0432.CCR-15-0530] [PMID: 26362997]
[15]
Remiszewski S. The discovery of NVP-LAQ824: From concept to clinic. Curr Med Chem 2003; 10(22): 2393-402.
[http://dx.doi.org/10.2174/0929867033456675] [PMID: 14529481]
[16]
Dai Y, Guo Y, Guo J, et al. Indole amide hydroxamic acids as potent inhibitors of histone deacetylases. Bioorg Med Chem Lett 2003; 13(11): 1897-901.
[http://dx.doi.org/10.1016/S0960-894X(03)00301-9] [PMID: 12749893]
[17]
Giannini G, Marzi M, Marzo MD, et al. Exploring bis-(indolyl)methane moiety as an alternative and innovative CAP group in the design of histone deacetylase (HDAC) inhibitors. Bioorg Med Chem Lett 2009; 19(10): 2840-3.
[http://dx.doi.org/10.1016/j.bmcl.2009.03.101] [PMID: 19359173]
[18]
Zhang Y, Yang P, Chou CJ, Liu C, Wang X, Xu W. Development of N-hydroxycinnamamide-based histone deacetylase inhibitors with an indole-containing cap group. ACS Med Chem Lett 2013; 4(2): 235-8.
[http://dx.doi.org/10.1021/ml300366t] [PMID: 23493449]
[19]
Li X, Inks ES, Li X, et al. Discovery of the first N-hydroxycinnamamide-based histone deacetylase 1/3 dual inhibitors with potent oral antitumor activity. J Med Chem 2014; 57(8): 3324-41.
[http://dx.doi.org/10.1021/jm401877m] [PMID: 24694055]
[20]
Li X, Wu J, Li X, et al. Development of N-hydroxybenzamide derivatives with indole-containing cap group as histone deacetylases inhibitors. Bioorg Med Chem 2015; 23(19): 6258-70.
[http://dx.doi.org/10.1016/j.bmc.2015.08.040] [PMID: 26349626]
[21]
Cai M, Hu J, Tian JL, Yan H, Zheng CG, Hu WL. Novel hybrids from N-hydroxyarylamide and indole ring through click chemistry as histone deacetylase inhibitors with potent antitumor activities. Chin Chem Lett 2015; 26(6): 675-80.
[http://dx.doi.org/10.1016/j.cclet.2015.03.015]
[22]
Liu T, Liu PY, Marshall GM. The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res 2009; 69(5): 1702-5.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-3365] [PMID: 19244112]
[23]
Luo J, Su F, Chen D, Shiloh A, Gu W. Deacetylation of p53 modulates its effect on cell growth and apoptosis. Nature 2000; 408(6810): 377-81.
[http://dx.doi.org/10.1038/35042612] [PMID: 11099047]
[24]
Yeung F, Hoberg JE, Ramsey CS, et al. Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J 2004; 23(12): 2369-80.
[http://dx.doi.org/10.1038/sj.emboj.7600244] [PMID: 15152190]
[25]
Brunet A, Sweeney LB, Sturgill JF, et al. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 2004; 303(5666): 2011-5.
[http://dx.doi.org/10.1126/science.1094637] [PMID: 14976264]
[26]
Spinck M, Bischoff M, Lampe P, Meyer-Almes FJ, Sievers S, Neumann H. Discovery of dihydro-1, 4-benzoxazine carboxamides as potent and highly selective inhibitors of sirtuin-1. J Med Chem 2021; 64(9): 5838-49.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00017] [PMID: 33876629]
[27]
Broussy S, Laaroussi H, Vidal M. Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat). J Enzyme Inhib Med Chem 2020; 35(1): 1124-36.
[http://dx.doi.org/10.1080/14756366.2020.1758691] [PMID: 32366137]
[28]
Layek M, Syam Kumar Y, Islam A, et al. Alkynylation of N-(3-iodopyridin-2-yl)sulfonamide under Pd/C–Cu catalysis: A direct one pot synthesis of 7-azaindoles and their pharmacological evaluation as potential inhibitors of sirtuins. MedChemComm 2011; 2(6): 478-85.
[http://dx.doi.org/10.1039/c1md00029b]
[29]
Panathur N, Dalimba U, Koushik PV, et al. Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition. Eur J Med Chem 2013; 69: 125-38.
[http://dx.doi.org/10.1016/j.ejmech.2013.08.018] [PMID: 24013412]
[30]
Manjula R, Gokhale N, Unni S, et al. Design, synthesis, in-vitro evaluation and molecular docking studies of novel indole derivatives as inhibitors of SIRT1 and SIRT2. Bioorg Chem 2019; 92: 103281.
[http://dx.doi.org/10.1016/j.bioorg.2019.103281] [PMID: 31561106]
[31]
Vojacek S, Schulig L, Wössner N, et al. Tetrahydroindoles as multipurpose screening compounds and novel sirtuin inhibitors. ChemMedChem 2019; 14(8): 853-64.
[http://dx.doi.org/10.1002/cmdc.201900054] [PMID: 30811852]
[32]
Feng Y, Teng X, Gu J, Yu B, Luo Y, Ye L. Novel anti-cancer agents: Design, synthesis, biological activity, molecular docking, and MD simulations of 2, 3, 4, 5-tetrahydro-1H-pyrido-[4,3-b]indole derivatives. Med Chem Res 2019; 28(2): 133-42.
[http://dx.doi.org/10.1007/s00044-018-2271-0]
[33]
Rambabu D, Raja G, Yogi Sreenivas B, et al. Spiro heterocycles as potential inhibitors of SIRT1: Pd/C-mediated synthesis of novel N-indolylmethyl spiroindoline-3,2′-quinazolines. Bioorg Med Chem Lett 2013; 23(5): 1351-7.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.089] [PMID: 23410798]
[34]
Mahajan SS, Scian M, Sripathy S, et al. Development of pyrazolone and isoxazol-5-one cambinol analogues as sirtuin inhibitors. J Med Chem 2014; 57(8): 3283-94.
[http://dx.doi.org/10.1021/jm4018064] [PMID: 24697269]
[35]
Panathur N, Gokhale N, Dalimba U, Koushik PV, Yogeeswari P, Sriram D. New indole–isoxazolone derivatives: Synthesis, characterisation and in vitro SIRT1 inhibition studies. Bioorg Med Chem Lett 2015; 25(14): 2768-72.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.015] [PMID: 26025875]
[36]
Zhang Z, Zhang R. p53-independent activities of MDM2 and their relevance to cancer therapy. Curr Cancer Drug Targets 2005; 5(1): 9-20.
[http://dx.doi.org/10.2174/1568009053332618] [PMID: 15720185]
[37]
Jones SN, Hancock AR, Vogel H, Donehower LA, Bradley A. Overexpression of Mdm2 in mice reveals a p53-independent role for Mdm2 in tumorigenesis. Proc Natl Acad Sci USA 1998; 95(26): 15608-12.
[http://dx.doi.org/10.1073/pnas.95.26.15608] [PMID: 9861017]
[38]
Miles X, Vandevoorde C, Hunter A, Bolcaen J. MDM2/X Inhibitors as Radiosensitizers for Glioblastoma Targeted Therapy. Front Oncol 2021; 11: 703442.
[http://dx.doi.org/10.3389/fonc.2021.703442] [PMID: 34307171]
[39]
Boettcher A, Buschmann N, Furet P, et al. 3-imidazolyl-indoles for the treatment of proliferative diseases. US Patent 6,699,883 B1, 2011.
[40]
Dömling A, Beck B. Preparation of pyrrolylimidazoles as antibiotics and antitumor agents. WO2001025213, 2001.
[41]
Popowicz GM, Czarna A, Wolf S, et al. Structures of low molecular weight inhibitors bound to MDMX and MDM2 reveal new approaches for p53-MDMX/MDM2 antagonist drug discovery. Cell Cycle 2010; 9(6): 1104-11.
[http://dx.doi.org/10.4161/cc.9.6.10956] [PMID: 20237429]
[42]
Wang W, Qin JJ, Voruganti S, et al. The pyrido[b]indole MDM2 inhibitor SP-141 exerts potent therapeutic effects in breast cancer models. Nat Commun 2014; 5(1): 5086.
[http://dx.doi.org/10.1038/ncomms6086] [PMID: 25271708]
[43]
Byl JAW, Cline SD, Utsugi T, Kobunai T, Yamada Y, Osheroff N. DNA topoisomerase II as the target for the anticancer drug TOP-53: Mechanistic basis for drug action. Biochemistry 2001; 40(3): 712-8.
[http://dx.doi.org/10.1021/bi0021838] [PMID: 11170388]
[44]
Li AL, Hao Y, Wang WY, Liu QS, Sun Y, Gu W. Design, synthesis, and anticancer evaluation of novel indole derivatives of ursolic acid as potential topoisomerase II inhibitors. Int J Mol Sci 2020; 21(8): 2876.
[http://dx.doi.org/10.3390/ijms21082876] [PMID: 32326071]
[45]
Chaniyara R, Tala S, Chen CW, et al. Novel antitumor indolizino[6,7-b]indoles with multiple modes of action: DNA cross-linking and topoisomerase I and II inhibition. J Med Chem 2013; 56(4): 1544-63.
[http://dx.doi.org/10.1021/jm301788a] [PMID: 23360284]
[46]
Song YL, Dong YF, Yang T, et al. Synthesis and pharmacological evaluation of novel bisindolylalkanes analogues. Bioorg Med Chem 2013; 21(24): 7624-7.
[http://dx.doi.org/10.1016/j.bmc.2013.10.034] [PMID: 24262885]
[47]
Barrows L, Radisky D, Copp B, et al. Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors. Anticancer Drug Des 1993; 8(5): 333-47.
[48]
Nadkarni D, Wang F, Wang W, et al. Synthesis and in vitro anti-lung cancer activity of novel 1, 3, 4, 8-tetrahydropyrrolo [4, 3, 2-de]quinolin-8(1H)-one alkaloid analogs. Med Chem 2009; 5(3): 227-36.
[http://dx.doi.org/10.2174/157340609788185873] [PMID: 19442212]
[49]
Vann KR, Ergün Y, Zencir S, Oncuoglu S, Osheroff N, Topcu Z. Inhibition of human DNA topoisomerase IIα by two novel ellipticine derivatives. Bioorg Med Chem Lett 2016; 26(7): 1809-12.
[http://dx.doi.org/10.1016/j.bmcl.2016.02.034] [PMID: 26906637]
[50]
Kaur R, Kaur G, Gill RK, Soni R, Bariwal J. Recent developments in tubulin polymerization inhibitors: An overview. Eur J Med Chem 2014; 87: 89-124.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.051] [PMID: 25240869]
[51]
Goel B, Jaiswal S, Jain S K. Indole derivatives targeting colchicine binding site as potential anticancer agents. Arch Pharm 2023; 356(10)
[http://dx.doi.org/10.1002/ardp.202300210]
[52]
Li L, Jiang S, Li X, Liu Y, Su J, Chen J. Recent advances in trimethoxyphenyl (TMP) based tubulin inhibitors targeting the colchicine binding site. Eur J Med Chem 2018; 151: 482-94.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.011] [PMID: 29649743]
[53]
Bacher G, Nickel B, Emig P, et al. D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity. Cancer Res 2001; 61(1): 392-9.
[PMID: 11196193]
[54]
Tahir SK, Nukkala MA, Zielinski Mozny NA, et al. Biological activity of A-289099: An orally active tubulin-binding indolyloxazoline derivative. Mol Cancer Ther 2003; 2(3): 227-33.
[PMID: 12657717]
[55]
Cong H, Zhao X, Castle BT, et al. An indole–chalcone inhibits multidrug-resistant cancer cell growth by targeting microtubules. Mol Pharm 2018; 15(9): 3892-900.
[http://dx.doi.org/10.1021/acs.molpharmaceut.8b00359] [PMID: 30048137]
[56]
Hu MJ, Zhang B, Yang HK, et al. Design, synthesis and molecular docking studies of novel indole–pyrimidine hybrids as tubulin polymerization inhibitors. Chem Biol Drug Des 2015; 86(6): 1491-500.
[http://dx.doi.org/10.1111/cbdd.12616] [PMID: 26177395]
[57]
Wienecke A, Bacher G. Indibulin, a novel microtubule inhibitor, discriminates between mature neuronal and nonneuronal tubulin. Cancer Res 2009; 69(1): 171-7.
[http://dx.doi.org/10.1158/0008-5472.CAN-08-1342] [PMID: 19118000]
[58]
Colley HE, Muthana M, Danson SJ, et al. An orally bioavailable, indole-3-glyoxylamide based series of tubulin polymerization inhibitors showing tumor growth inhibition in a mouse xenograft model of head and neck cancer. J Med Chem 2015; 58(23): 9309-33.
[http://dx.doi.org/10.1021/acs.jmedchem.5b01312] [PMID: 26580420]
[59]
Zhang YL, Qin YJ, Tang DJ, et al. Synthesis and Biological Evaluation of 1-Methyl-1 H -indole-Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors. ChemMedChem 2016; 11(13): 1446-58.
[http://dx.doi.org/10.1002/cmdc.201600137] [PMID: 27159418]
[60]
Sri Ramya PV, Angapelly S, Guntuku L, et al. Synthesis and biological evaluation of curcumin inspired indole analogues as tubulin polymerization inhibitors. Eur J Med Chem 2017; 127: 100-14.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.043] [PMID: 28038323]
[61]
Li W, Yin Y, Yao H, et al. Discovery of novel vinyl sulfone derivatives as anti-tumor agents with microtubule polymerization inhibitory and vascular disrupting activities. Eur J Med Chem 2018; 157: 1068-80.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.074] [PMID: 30176537]
[62]
Li W, Sun H, Xu F, et al. Synthesis, molecular properties prediction and biological evaluation of indole-vinyl sulfone derivatives as novel tubulin polymerization inhibitors targeting the colchicine binding site. Bioorg Chem 2019; 85: 49-59.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.015] [PMID: 30599412]
[63]
Hwang DJ, Wang J, Li W, Miller DD. Structural optimization of indole derivatives acting at colchicine binding site as potential anticancer agents. ACS Med Chem Lett 2015; 6(9): 993-7.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00208] [PMID: 26396686]
[64]
Bose C, Banerjee P, Kundu J, et al. Evaluation of a tubulin‐targeted pyrimidine indole hybrid molecule as an anticancer agent. ChemistrySelect 2020; 5(44): 14021-31.
[http://dx.doi.org/10.1002/slct.202003322]
[65]
Hawash M, Kahraman DC, Olgac A, et al. Design and synthesis of novel substituted indole-acrylamide derivatives and evaluation of their anti-cancer activity as potential tubulin-targeting agents. J Mol Struct 2022; 1254: 132345.
[http://dx.doi.org/10.1016/j.molstruc.2022.132345]
[66]
Yang F, Jian XE, Chen L, et al. Discovery of new indole-based 1,2,4-triazole derivatives as potent tubulin polymerization inhibitors with anticancer activity. New J Chem 2021; 45(46): 21869-80.
[http://dx.doi.org/10.1039/D1NJ03892C]
[67]
Kode J, Kovvuri J, Nagaraju B, et al. Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors. Bioorg Chem 2020; 105: 104447.
[http://dx.doi.org/10.1016/j.bioorg.2020.104447] [PMID: 33207276]
[68]
Lai MJ, Ojha R, Lin MH, et al. 1-Arylsulfonyl indoline-benzamides as a new antitubulin agents, with inhibition of histone deacetylase. Eur J Med Chem 2019; 162: 612-30.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.066] [PMID: 30476825]
[69]
Wan Y, He S, Li W, Tang Z. Indazole derivatives: Promising anti-tumor agents. Anticancer Agents Med Chem 2019; 18(9): 1228-34.
[http://dx.doi.org/10.2174/1871520618666180510113822] [PMID: 29745343]
[70]
Ardito F, Giuliani M, Perrone D, Troiano G, Muzio LL. The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review). Int J Mol Med 2017; 40(2): 271-80.
[http://dx.doi.org/10.3892/ijmm.2017.3036] [PMID: 28656226]
[71]
Fraley ME, Arrington KL, Bilodeau MT, et al. Tyrosine kinase inhibitors. US Patent 6,306,874, 2001.
[72]
Lo H, Wang A, Zhang Q. Indolinone derivative as tyrosine kinase inhibitor. US Patent 9642851B2, 2017.
[73]
Glaenzel U, Nufer R. Pyrimidin-4-yl)oxy)-1h-indole-1-carboxamide derivatives and use thereof. WO2014184778A1, 2017.
[74]
Rathi AK, Syed R, Singh V, Shin HS, 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]
[75]
Lee O, Hwang C-S, Chen C-H, et al. Polymer drug conjugates with tether groups for controlled drug delivery. US Patent 9610360, 2010.
[76]
Mesaros EF, Ott GR, Dorsey BD. Anaplastic lymphoma kinase inhibitors as anticancer therapeutics: A patent review. Expert Opin Ther Pat 2014; 24(4): 417-42.
[http://dx.doi.org/10.1517/13543776.2014.877890] [PMID: 24476492]
[77]
Purandare AV, Batt DG, Liu Q, Mastalerz H, Zimmermann K. Carbazole and carboline kinase inhibitors. US Patent 8815840, 2014.
[78]
N’guyen C-H, Molla A. Amino-substituted-alkyloxybenzo[e]pyrido[4,3-b]indole derivatives as new potent kinase inhibitors. US Patent 20140073637, 2014.
[79]
Vanotti E, Caldarelli M, Casuscelli F, et al. Tricyclic indoles and (4,5-dihydro) indoles. US Patent 8207180, 2012.
[80]
Brault L, Gasser C, Bracher F, Huber K, Knapp S, Schwaller J. PIM serine/threonine kinases in the pathogenesis and therapy of hematologic malignancies and solid cancers. Haematologica 2010; 95(6): 1004-15.
[http://dx.doi.org/10.3324/haematol.2009.017079] [PMID: 20145274]
[81]
Asati V, Mahapatra DK, Bharti SK. Thiazolidine-2,4-diones as multi-targeted scaffold in medicinal chemistry: Potential anticancer agents. Eur J Med Chem 2014; 87: 814-33.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.025] [PMID: 25440883]
[82]
Nishiguchi GA, Atallah G, Bellamacina C, et al. Discovery of novel 3,5-disubstituted indole derivatives as potent inhibitors of Pim-1, Pim-2, and Pim-3 protein kinases. Bioorg Med Chem Lett 2011; 21(21): 6366-9.
[http://dx.doi.org/10.1016/j.bmcl.2011.08.105] [PMID: 21945284]
[83]
More KN, Jang HW, Hong VS, Lee J. Pim kinase inhibitory and antiproliferative activity of a novel series of meridianin C derivatives. Bioorg Med Chem Lett 2014; 24(11): 2424-8.
[http://dx.doi.org/10.1016/j.bmcl.2014.04.035] [PMID: 24775304]
[84]
Smith IE, Dowsett M. Aromatase inhibitors in breast cancer. N Engl J Med 2003; 348(24): 2431-42.
[http://dx.doi.org/10.1056/NEJMra023246] [PMID: 12802030]
[85]
Ozcan-Sezer S, Ince E, Akdemir A, Ceylan ÖÖ, Suzen S, Gurer-Orhan H. Aromatase inhibition by 2-methyl indole hydrazone derivatives evaluated via molecular docking and in vitro activity studies. Xenobiotica 2019; 49(5): 549-56.
[http://dx.doi.org/10.1080/00498254.2018.1482029] [PMID: 29804490]
[86]
Pingaew R, Mandi P, Prachayasittikul V, Prachayasittikul S, Ruchirawat S, Prachayasittikul V. Synthesis, molecular docking, and QSAR study of sulfonamide-based indoles as aromatase inhibitors. Eur J Med Chem 2018; 143: 1604-15.
[http://dx.doi.org/10.1016/j.ejmech.2017.10.057] [PMID: 29137864]
[87]
Fantacuzzi M, De Filippis B, Gallorini M, et al. Synthesis, biological evaluation, and docking study of indole aryl sulfonamides as aromatase inhibitors. Eur J Med Chem 2020; 185: 111815.
[http://dx.doi.org/10.1016/j.ejmech.2019.111815] [PMID: 31732252]
[88]
Begum S, Jaswanthi P, Venkata Lakshmi B, Bharathi K. QSAR studies on indole-azole Analogues using DTC tools; imidazole ring is more favorable for aromatase inhibition. J Indian Chem Soc 2021; 98(1): 100016.
[http://dx.doi.org/10.1016/j.jics.2021.100016]
[89]
Alzahrani AS. PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. In: Semin Cancer Biol. 2019; 59: pp. 125-32.
[90]
Heydari P, Noroozi K. Assessment of the Regulatory Effect of Novel Indole-Core-Based Compound on Apoptosis and Cell Survival of Acute Myeloid Leukemia Cell Line. Iran Red Crescent Med J 2021; 23(8): 100016.
[91]
Kumar S, Guru SK, Pathania AS, et al. Fascaplysin induces caspase mediated crosstalk between apoptosis and autophagy through the inhibition of PI3K/AKT/mTOR signaling cascade in human leukemia HL-60 cells. J Cell Biochem 2015; 116(6): 985-97.
[http://dx.doi.org/10.1002/jcb.25053] [PMID: 25561006]
[92]
Sharma S, Guru SK, Manda S, et al. A marine sponge alkaloid derivative 4-chloro fascaplysin inhibits tumor growth and VEGF mediated angiogenesis by disrupting PI3K/Akt/mTOR signaling cascade. Chem Biol Interact 2017; 275: 47-60.
[http://dx.doi.org/10.1016/j.cbi.2017.07.017] [PMID: 28756150]
[93]
Abe A, Kokuba H. Harmol induces autophagy and subsequent apoptosis in U251MG human glioma cells through the downregulation of survivin. Oncol Rep 2013; 29(4): 1333-42.
[http://dx.doi.org/10.3892/or.2013.2242] [PMID: 23338618]
[94]
Li C, Wang Y, Wang C, Yi X, Li M, He X. Anticancer activities of harmine by inducing a pro-death autophagy and apoptosis in human gastric cancer cells. Phytomedicine 2017; 28: 10-8.
[http://dx.doi.org/10.1016/j.phymed.2017.02.008] [PMID: 28478808]
[95]
Ding Y, Wang B, Chen X, Zhou Y, Ge J. Staurosporine suppresses survival of HepG2 cancer cells through Omi/HtrA2-mediated inhibition of PI3K/Akt signaling pathway. Tumour Biol 2017; 39(3)
[http://dx.doi.org/10.1177/1010428317694317] [PMID: 28349827]
[96]
Wang Y, Wang L, Guan S, et al. Novel ALK inhibitor AZD3463 inhibits neuroblastoma growth by overcoming crizotinib resistance and inducing apoptosis. Sci Rep 2016; 6(1): 19423.
[http://dx.doi.org/10.1038/srep19423] [PMID: 26786851]
[97]
Chakraborty S, Ghosh S, Banerjee B, et al. Phemindole, a synthetic di-indole derivative maneuvers the store operated calcium entry (SOCE) to induce potent anti-carcinogenic activity in human triple negative breast cancer cells. Front Pharmacol 2016; 7: 114.
[http://dx.doi.org/10.3389/fphar.2016.00114] [PMID: 27199756]
[98]
Nguyen P, Doan P, Rimpilainen T, et al. Synthesis and preclinical validation of novel indole derivatives as a GPR17 agonist for glioblastoma treatment. J Med Chem 2021; 64(15): 10908-18.
[http://dx.doi.org/10.1021/acs.jmedchem.1c00277] [PMID: 34304559]
[99]
Singh AA, Patil MP, Kang MJ, Niyonizigiye I, Kim GD. Biomedical application of Indole-3-carbinol: A mini-review. Phytochem Lett 2021; 41: 49-54.
[http://dx.doi.org/10.1016/j.phytol.2020.09.024]
[100]
Guo C, Liu F, Qi J, et al. A novel synthetic dihydroindeno [1, 2-b] indole derivative (LS-2-3j) reverses ABCB1-and ABCG2-mediated multidrug resistance in cancer cells. Molecules 2018; 23(12): 3264.
[http://dx.doi.org/10.3390/molecules23123264] [PMID: 30544754]
[101]
Russo E, Grondona C, Brullo C, Spallarossa A, Villa C, Tasso B. Indole antitumor agents in nanotechnology formulations: An overview. Pharmaceutics 2023; 15(7): 1815.
[http://dx.doi.org/10.3390/pharmaceutics15071815] [PMID: 37514002]
[102]
Golombek SK, May JN, Theek B, et al. Tumor targeting via EPR: Strategies to enhance patient responses. Adv Drug Deliv Rev 2018; 130: 17-38.
[http://dx.doi.org/10.1016/j.addr.2018.07.007] [PMID: 30009886]
[103]
Torchilin V. Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur J Pharm Biopharm 2009; 71(3): 431-44.
[http://dx.doi.org/10.1016/j.ejpb.2008.09.026] [PMID: 18977297]
[104]
Huang L, Guo S. Nanoparticles escaping RES and endosome: Challenges for SiRNA delivery for cancer therapy. J Nanomater 2011; 2011: 11.
[105]
Charkhat Gorgich EA, Kasbiyan H, Shabani R, et al. Smart chlorotoxin-functionalized liposomes for sunitinib targeted delivery into glioblastoma cells. J Drug Deliv Sci Technol 2022; 77: 103908.
[http://dx.doi.org/10.1016/j.jddst.2022.103908]
[106]
Lai X, Liu XL, Pan H, et al. Light-triggered efficient sequential drug delivery of biomimetic nanosystem for multimodal chemo-, antiangiogenic, and anti-MDSC therapy in melanoma. Adv Mater 2022; 34(10): 2106682.
[http://dx.doi.org/10.1002/adma.202106682] [PMID: 34989039]
[107]
Joseph JJ, Sangeetha D, Gomathi T. Sunitinib loaded chitosan nanoparticles formulation and its evaluation. Int J Biol Macromol 2016; 82: 952-8.
[http://dx.doi.org/10.1016/j.ijbiomac.2015.10.079] [PMID: 26522243]
[108]
Torabi M, Aghanejad A, Savadi P, Barzegari A, Omidi Y, Barar J. Targeted delivery of sunitinib by MUC-1 aptamer-capped magnetic mesoporous silica nanoparticles. Molecules 2023; 28(1): 411.
[http://dx.doi.org/10.3390/molecules28010411] [PMID: 36615606]
[109]
Ahmed MM, Anwer MK, Fatima F, et al. Boosting the anticancer activity of sunitinib malate in breast cancer through lipid polymer hybrid nanoparticles approach. Polymers (Basel) 2022; 14(12): 2459.
[http://dx.doi.org/10.3390/polym14122459] [PMID: 35746034]
[110]
Braatz D, Dimde M, Ma G, et al. Toolbox of biodegradable dendritic (poly glycerol sulfate)-ss-poly(ester) micelles for cancer treatment: Stability, drug release, and tumor targeting. Biomacromolecules 2021; 22(6): 2625-40.
[http://dx.doi.org/10.1021/acs.biomac.1c00333] [PMID: 34076415]
[111]
Xu Y, Liu Y, Liu Q, et al. Co-delivery of bufalin and nintedanib via albumin sub-microspheres for synergistic cancer therapy. J Control Release 2021; 338: 705-18.
[http://dx.doi.org/10.1016/j.jconrel.2021.08.049] [PMID: 34481023]
[112]
Zha Q, Zhang L, Guo Y, Bao R, Shi F, Shi Y. Preparation and study of folate modified albumin targeting microspheres. J Oncol 2022; 2022: 1-9.
[http://dx.doi.org/10.1155/2022/3968403] [PMID: 35126516]
[113]
Xu Y, Liu Y, He T, et al. Biguanides decorated albumin nanoparticles loading nintedanib for synergic enhanced hepatocellular carcinoma therapy. Colloids Surf B Biointerfaces 2021; 207: 112020.
[http://dx.doi.org/10.1016/j.colsurfb.2021.112020] [PMID: 34403984]
[114]
Zhang Y, Chen H, Feng N, et al. Construction and antitumor effects of antitumor micelles with cyclic RGD-modified anlotinib. Nanomedicine 2020; 28: 102224.
[http://dx.doi.org/10.1016/j.nano.2020.102224] [PMID: 32428675]

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