Kanser Çoklu İlaç Dirençliliğinin Yenilmesinde İmidazopiridinler: Yeni Umutlar

Yıl 2024, Cilt: 6 Sayı: 2, 216 - 225, 30.06.2024

Cevriye Yıldırım , Erkan Yurtcu

https://doi.org/10.52827/hititmedj.1425486

Öz

Kanser tedavisinde kullanılan farmakoterapi protokolleri ilaçlara bağlı toksisite ve ilacın etkinliğinin azalması gibi nedenlerden ötürü birçok hasta için tedavi edici olmaktan uzaktır. Çoklu ilaç direnci kanser hücresinin birbirinden farklı ilaç gruplarına ya da ilaç kombinasyonlarına karşı geliştirdiği bir savunma mekanizmasıdır. En önemli nedenlerinden biri hücreden ilaç atımını sağlayan ABC taşıyıcılarının etkinliğinin ya da sayısının artmasıdır. Birçok biyomolekülün yapısına katılan imidazopiridinler uzun yıllardır laboratuvar koşullarında üretilebilmektedirler. İmidazopiridinler kanser hücrelerini çeşitli yollarla öldürebilen etkin antikanser ajanlardır. Bu derlemede imidazopiridinlerin kanser hücrelerinde ABC taşıyıcılarını hedefleyerek çoklu ilaç direncinin üstesinden gelinmesinde kullanıldığı çalışmaların ayrıntılı bir özetini sunduk. Bu amaçla sentezlenen ve ilaç olarak kullanılan ajanlar ile henüz klinik denemelerine başlanmamış bileşiklerin sentezlenme stratejilerini ve laboratuvar sonuçlarını toplu halde değerlendirdik. Birkaç imidazopiridin türevinin reçete edilebilen ilaçlar olarak piyasaya sunulması bu moleküllerin potansiyelini yansıtmaktadır. Hedefe yönelik tedavi sağlayabilen ajanların klinikte daha sık kullanılacağını ve tedavi başarılarını iyileştireceğini düşünüyoruz.

Anahtar Kelimeler

ABC Taşıyıcılar, çoklu ilaç direnci, imidazopiridin, kanser

Imidazopyridines in Overcoming Cancer Multidrug Resistance: New Hopes

Öz

Pharmacotherapy protocols used in cancer treatment are far from curative for many patients due to reasons such as drug-related toxicity and decreased effectiveness of the drug. Multidrug resistance is a defense mechanism developed by the cancer cell against different drug groups or drug combinations. One of the most important reasons is the increase in the efficiency or number of ABC transporters that ensure drug removal from the cell. Imidazopyridines, which are incorporated into the structure of many biomolecules, have been produced under laboratory conditions for many years. Imidazopyridines are effective anticancer agents that can kill cancer cells in various ways. In this review, we presented a detailed summary of studies in which imidazopyridines were used to overcome multidrug resistance by targeting ABC transporters in cancer cells. For this purpose, we collectively evaluated the synthesis strategies and laboratory results of the agents synthesized and used as drugs and the compounds whose clinical trials have not yet started. The introduction of several imidazopyridine derivatives as prescription drugs reflects the potential of these molecules. We think that agents that can provide targeted therapy will be used more frequently in the clinic and will improve treatment success.

Anahtar Kelimeler

ABC Transporters, cancer, imidazopyridine, multidrug resistance

Kaynakça

• Wild CP, Weiderpass E, Stewart BW, editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer. Available from: http://publications.iarc.fr/586. Licence: CC BY-NC-ND 3.0 IGO
• Li T, Li J, Chen Z, et al. Glioma diagnosis and therapy: Current challenges and nanomaterial-based solutions. Journal of Controlled Release 2022;1(352):338–370.
• Seebacher NA, Stacy AE, Porter GM, Merlot AM. Clinical development of targeted and immune based anti-cancer therapies. Journal of Experimental & Clinical Cancer Research 2019;1138(1):156.
• Rana A, Alex JM, Chauhan M, Joshi G, Kumar R. A review on pharmacophoric designs of antiproliferative agents. Med Chem Res 2015;1:24(3):903–920.
• Altaher AMH, Adris MA, Aliwaini SH. Imidazo[1,2-a]pyridine Based Compounds: The Hopeful Anti-Cancer Therapy. Cancer Therapy 2021;12(4):79-85.
• Tacar O, Sriamornsak P, Dass CR. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems. Journal of Pharmacy and Pharmacology 2013;1:65(2):157–170.
• Komeili-Movahhed T, Fouladdel S, Barzegar E, et al. PI3K/ Akt inhibition and down-regulation of BCRP re-sensitize MCF7 breast cancer cell line to mitoxantrone chemotherapy. Iran J Basic Med Sci 2015;18(5):472–477.
• Zahreddine H, Borden KLB. Mechanisms and insights into drug resistance in cancer. Front Pharmacol 2013;14(4):1-8.
• Housman G, Byler S, Heerboth S, et al. Drug Resistance in Cancer: An Overview. Cancers (Basel). 2014;5:6(3):1769–92.
• Hanssen KM, Haber M, Fletcher JI. Targeting multidrug resistance-associated protein 1 (MRP1)-expressing cancers: Beyond pharmacological inhibition. Drug Resistance Updates 2021;1(59):100795.
• Assaraf YG, Brozovic A, Gonçalves AC, et al. The multi-factorial nature of clinical multidrug resistance in cancer. Drug Resistance Updates 2019;1(46):100645.
• Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. International Journal of Molecular Sciences 2020;21(9):3233.
• Zhitomirsky B, Assaraf YG. Lysosomes as mediators of drug resistance in cancer. Drug Resistance Updates 2016;1:(24):23–33.
• Ween MP, Armstrong MA, Oehler MK, Ricciardelli C. The role of ABC transporters in ovarian cancer progression and chemoresistance. Critical Reviews in Oncology/Hematology 2015; 1;96(2):220–256.
• Fletcher JI, Williams RT, Henderson MJ, Norris MD, Haber M. ABC transporters as mediators of drug resistance and contributors to cancer cell biology. Drug Resistance Updates 2016;1(26):1–9.
• Wang JQ, Yang Y, Cai CY, et al. Multidrug resistance proteins (MRPs): Structure, function and the overcoming of cancer multidrug resistance. Drug Resistance Updates 2021;1(54):100743.
• Li W, Zhang H, Assaraf YG, et al. Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies. Drug Resistance Updates 2016;1(27):14–29.
• Bakar E, Gülyenli DÖ. Dışa Atım Pompa Sistemleri ve Bu Sistemlerin Kanser Tedavisindeki Etkinlikleri. Adnan Menderes Üniversitesi Sağlık Bilimleri Fakültesi Dergisi 2019;31;3(1):54–69.
• Tamaki A, Ierano C, Szakacs G, Robey RW, Bates SE. The controversial role of ABC transporters in clinical oncology. Sharom FJ, editor. Essays in Biochemistry 2011;7(50):209–232.
• Yu M, Ocana A, Tannock IF. Reversal of ATP-binding cassette drug transporter activity to modulate chemoresistance: why has it failed to provide clinical benefit? Cancer Metastasis Rev 2013;1:32(1):211–227.
• Verma A, Joshi S, Singh D. Imidazole: Having Versatile Biological Activities. Journal of Chemistry 2013;31:2013e329412.
• Zhang L, Peng XM, Damu GLV, Geng RX, Zhou CH. Comprehensive Review in Current Developments of Imidazole- Based Medicinal Chemistry. Medicinal Research Reviews 2014;34(2):340–437.
• Aleksandrova EV, Kravchenko AN, Kochergin PM. Properties of haloimidazoles (review). Chem Heterocycl Comp 2011;1:47(3):261– 89.
• Bagdi AK, Santra S, Monir K, Hajra A. Synthesis of imidazo[1,2-a]pyridines: a decade update. Chem Commun 2015;15:51(9):1555–1575.
• Khatun S, Singh A, Bader GN, Sofi FA. Imidazopyridine, a promising scaffold with potential medicinal applications and structural activity relationship (SAR): recent advances. Journal of Biomolecular Structure and Dynamics 2022;26:40(24):14279– 14302.
• Krause M, Foks H, Gobis K. Pharmacological Potential and Synthetic Approaches of Imidazo[4,5-b]pyridine and Imidazo[4,5-c]pyridine Derivatives. Molecules 2017;4:22(3):399.
• Edvinsson L, Linde M. New drugs in migraine treatment and prophylaxis: telcagepant and topiramate. The Lancet 2010;21:376(9741):645–655.
• Scarpignato C, Hunt RH. Proton pump inhibitors: the beginning of the end or the end of the beginning? Current Opinion in Pharmacology 2008;1:8(6):677–684.
• Vitaku E, Smith DT, Njardarson JT. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J Med Chem 2014;26:57(24):10257–10274.
• Morris PG, Fornier MN. Microtubule Active Agents: Beyond the Taxane Frontier. Clinical Cancer Research 2008;14:14(22):7167–172. Peytam F, Emamgholipour Z, Mousavi A, et al. Imidazopyridine-based kinase inhibitors as potential anticancer agents: A review. Bioorganic Chemistry 2023;1:106831.
• Sharma P, LaRosa C, Antwi J, Govindarajan R, Werbovetz KA. Imidazoles as Potential Anticancer Agents: An Update on Recent Studies. Molecules 2021;26(14):4213.
• James DA, Koya K, Li H, et al. Conjugated indole-imidazole derivatives displaying cytotoxicity against multidrug resistant cancer cell lines. Bioorganic & Medicinal Chemistry Letters 2006;1:16(19):5164–5168.
• 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;10:6(9):993–997.
• Arnst KE, Wang Y, Lei ZN, et al. Colchicine Binding Site Agent DJ95 Overcomes Drug Resistance and Exhibits Antitumor Efficacy. Mol Pharmacol 2019;1:96(1):73–89.
• Chan F, Sun C, Perumal M, et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Molecular Cancer Therapeutics 2007;18:6(12):3147–3157.
• Cheng C, Liu Z Guo, Zhang H, et al. Enhancing Chemosensitivity in ABCB1- and ABCG2-Overexpressing Cells and Cancer Stem-like Cells by An Aurora Kinase Inhibitor CCT129202. Mol Pharmaceutics 2012;2:9(7):1971–1982.
• Baviskar AT, Amrutkar SM, Trivedi N, et al. Switch in Site of Inhibition: A Strategy for Structure-Based Discovery of Human Topoisomerase IIα Catalytic Inhibitors. ACS Med Chem Lett 2015;9:6(4):481–485.
• Sajith AM, Abdul Khader KK, Joshi N, et al. Design, synthesis and structure–activity relationship (SAR) studies of imidazo[4,5-b]pyridine derived purine isosteres and their potential as cytotoxic agents. European Journal of Medicinal Chemistry 2015;7(89):21–31.
• Montagner D, Fresch B, Browne K, Gandin V, Erxleben A. A Cu (ii) complex targeting the translocator protein: in vitro and in vivo antitumor potential and mechanistic insights. Chemical Communications 2017;53(1):134–137.
• Bourichi S, Misbahi H, Rodi YK, et al. In Vitro Evaluation of the Multidrug Resistance Reversing Activity of Novel Imidazo[4,5-b]pyridine Derivatives. Anticancer Research 2018;1:38(7):3999–4003.
• Wang K, Ye K, Zhang X, et al. Dual Nicotinamide Phosphoribosyltransferase (NAMPT) and Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitors for the Treatment of Drug-Resistant Nonsmall-Cell Lung Cancer. J Med Chem 2023;12:66(1):1027–1047.
• Lee H, Jung KH, Jeong Y, Hong S, Hong SS. HS-173, a novel phosphatidylinositol 3-kinase (PI3K) inhibitor, has anti-tumor activity through promoting apoptosis and inhibiting angiogenesis. Cancer Letters 2013;1:328(1):152–159.
• Lee H, Kim SJ, Jung KH, et al. A novel imidazopyridine PI3K inhibitor with anticancer activity in non-small cell lung cancer cells. Oncology Reports 2013;1:30(2):863–869.
• Wu CP, Hung CY, Hsieh YJ, et al. ABCB1 and ABCG2 Overexpression Mediates Resistance to the Phosphatidylinositol 3-Kinase Inhibitor HS-173 in Cancer Cell Lines. Cells 2023;12(7):1056.