Design, synthesis, anticancer evaluation and molecular docking studies of new imidazo [2, 1-b] thiazole -based chalcones
Tóm tắt
A new series of imidazo[2, 1-b]thiazole-based chalcone derivatives were designed, synthesized, and tested for their anticancer activities. Firstly, the cytotoxic ability of the compounds was tested on three different types of cancer cells, namely colorectal adenocarcinoma (HT-29), lung carcinoma (A-549), breast adenocarcinoma (MCF-7), and mouse fibroblast cells (3T3-L1) by XTT tests. Afterwards, further anticancer activity studies with the compound 3j having the lowest IC50 and highest SI values were performed on MCF-7 cells. XTT results revealed that all the test compounds exhibited much higher cytotoxic activity on the cancer cells than that of normal 3T3-L1 cells. Among the compounds, 3j especially stood out with its IC50 (9.76 µM) and SI (14.99) values on MCF-7 cells. Flow cytometry analysis proved that 3j-treated MCF-7 cells was resulted in the mitochondrial membrane depolarization, multicaspase activation, and ultimately apoptosis. Additionally, in silico molecular docking approaches were carried out to confirm the experimental observations and investigate the efficacy of the compound 3j. The interactions of 3j on DNA dodecamer and caspase-3 were investigated by molecular docking studies. Based on these interactions, the active amino acids in the binding site were determined and their free binding energies (ΔGBind) were calculated.
Tài liệu tham khảo
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. Cancer J Clin. 2021;7:17. https://doi.org/10.3322/caac.21654.
Kobylinska L, Mitina N, Zaichenko A, Stoika R. Controlled delivery and reduced side effects of anticancer drugs complexed with polymeric nanocarrier. J. Biomed. Nanotechnol. 2022:119–47. https://doi.org/10.1007/978-3-030-76235-3_5.
Levi M, Sivapalaratnam S, Levi M, Sivapalaratnam S. An overview of thrombotic complications of old and new anticancer drugs. Thrombosis Res. 2020;191:S17–S21. https://doi.org/10.1016/S0049-3848(20)30391-1.
Ali I, Nadeem Lone M, Al-Othman ZA, Al-Warthan M, Marsin Sanagi M. Heterocyclic scaffolds: centrality in anticancer drug development. Curr Drug Targets. 2015;16:711–34.
Thari FZ, Tachallait H, El Alaoui N, Talha A, Arshad S, Álvarez E, et al. Ultrasound-assisted one-pot green synthesis of new N- substituted-5-arylidene-thiazolidine-2,4-dione-isoxazoline derivatives using NaCl/Oxone/Na3PO4 in aqueous media. Ultrason Sonochem. 2020;68:105222. https://doi.org/10.1016/j.ultsonch.2020.105222.
Talha A, Mourhly A, Tachallait H, Driowya M, El Hamidi A, Arshad S, et al. One-pot four-component tandem synthesis of novel sulfonamide-1, 2, 3-triazoles catalyzed by reusable copper (II)-adsorbed on mesoporous silica under ultrasound irradiation. Tetrahedron. 2021;90:132215. https://doi.org/10.1016/j.tet.2021.132215.
Kamal A, Dastagiri D, Ramaiah MJ, Reddy JS, Bharathi EV, Srinivas C, et al. Synthesis of imidazothiazole–chalcone derivatives as anticancer and apoptosis inducing agents. ChemMedChem. 2012;5:1937–1647. https://doi.org/10.1002/cmdc.201000346.
Abdel-Maksoud MS, Ammar UM, Oh CH. Anticancer profile of newly synthesized BRAF inhibitors possess 5-(pyrimidin-4-yl) imidazo [2, 1-b] thiazole scaffold. Bioorg Med Chem. 2019;27:2041–51. https://doi.org/10.1016/j.bmc.2019.03.062.
Shetty NS, Khazi IAM, Ahn C. Synthesis, anthelmintic and anti-inflammatory activities of some novel imidazothiazole sulfides and sulfones. Bull Korean Chem Soc. 2010;31:2337–40. https://doi.org/10.5012/bkcs.2010.31.8.2337.
Moraski GC, Deboosère N, Marshall KL, Weaver HA, Vandeputte A, Hastings C, et al. Intracellular and in vivo evaluation of imidazo[2,1-b]thiazole-5-carboxamide anti-tuberculosis compounds. PloS ONE. 2020;15:e0227224. https://doi.org/10.1371/journal.pone.0227224.
Gürsoy E, Dincel ED, Naesens L, Güzeldemirci NU. Design and synthesis of novel Imidazo [2, 1-b] thiazole derivatives as potent antiviral and antimycobacterial agents. Bioorg Chem. 2020;95:103496. https://doi.org/10.1016/j.bioorg.2019.103496.
Dincel ED, Gürsoy E, Yilmaz-Ozden T, Ulusoy-Güzeldemirci N. Antioxidant activity of novel imidazo[2,1-b]thiazole derivatives: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction. Bioorg Chem. 2020;103:104220. https://doi.org/10.1016/j.bioorg.2020.104220.
Koudad M, El Hamouti C, Elaatiaoui A, Dadou S, Oussaid A, Abrigach F, et al. Synthesis, crystal structure, antimicrobial activity and docking studies of new imidazothiazole derivatives. J Iran Chem Soc. 2020;17:297–306. https://doi.org/10.1007/s13738-019-01766-4.
Sultana F, Bonam SR, Reddy VG, Nayak VL, Akunuri R, Routhu SR, et al. Synthesis of benzo [d] imidazo [2, 1-b] thiazole-chalcone conjugates as microtubule targeting and apoptosis inducing agents. Bioorg Chem. 2018;76:1–12. https://doi.org/10.1016/j.bioorg.2017.10.019.
Shareef MA, Devi GP, Routhu SR, Kumar G, Kamal A, Babu BN. New imidazo [2, 1-b] thiazole-based aryl hydrazones: unravelling their synthesis and antiproliferative and apoptosis-inducing potential. RSC Med Chem. 2020;11:1178–84. https://doi.org/10.1039/D0MD00188K.
Singh P, Anand A, Kumar V. Recent developments in biological activities of chalcones: a mini review. Eur J Med Chem. 2014;85:758–77. https://doi.org/10.1016/j.ejmech.2014.08.033.
Katsori AM, Hadjipavlou-Litina D. Recent progress in therapeutic applications of chalcones. Expert Opin Ther Pat. 2011;21:1575–96. https://doi.org/10.1517/13543776.2011.596529.
Rani A, Anand A, Kumar K, Kumar V. Recent developments in biological aspects of chalcones: the odyssey continues. Expert Opin Drug Disco. 2019;14:249–88. https://doi.org/10.1080/17460441.2019.1573812.
Rocha S, Ribeiro D, Fernandes E, Freitas M. A systematic review on anti-diabetic properties of chalcones. Curr Med Chem. 2020;27:2257–321. https://doi.org/10.2174/0929867325666181001112226.
Salehi B, Quispe C, Chamkhi I, El Omari N, Balahbib A, Sharifi-Rad J, et al. Pharmacological properties of chalcones: a review of preclinical including molecular mechanisms and clinical evidence. Front Pharmacol 2020;11:592654. https://doi.org/10.3389/fphar.2020.592654.
Tabata K, Motani K, Takayanagi N, Nishimura R, Asami S, Kimura Y, et al. Xanthoangelol, a major chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma and leukemia cells. Biol Pharm Bull. 2005;28:1404–7. https://doi.org/10.1248/bpb.28.1404.
Zhang L, Chen W, Li X. A novel anticancer effect of butein: inhibition of invasion through the ERK1/2 and NF-κB signaling pathways in bladder cancer cells. FEBS Lett. 2008;582:1821–8. https://doi.org/10.1016/j.febslet.2008.04.046.
Akihisa T, Kikuchi T, Nagai H, Ishii K, Tabata K, Suzuki T. 4-Hydroxyderricin from Angelica keiskei roots induces caspase-dependent apoptotic cell death in HL60 human leukemia cells. J Oleo Sci. 2011;60:71–77. https://doi.org/10.5650/jos.60.71.
Zi X, Simoneau AR. Simoneau, Flavokawain A, a Novel Chalcone from Kava Extract, Induces apoptosis in bladder cancer cells by involvement of Bax Protein-Dependent and Mitochondria-Dependent apoptotic pathway and suppresses tumor growth in mice. Cancer Res. 2005;65:3479. https://doi.org/10.1158/0008-5472.CAN-04-3803.
Tabeshpour J, Sahebkar A, Zirak MR, Zeinali M, Hashemzaei M, Rakhshani S, et al. Computer-aided drug design and drug pharmacokinetic prediction: a mini-review. Curr Pharm Des. 2018;24:3014–9. https://doi.org/10.2174/1381612824666180903123423.
Altay A, Caglar S, Caglar B. Silver (I) complexes containing diclofenac and niflumic acid induce apoptosis in human-derived cancer cell lines. Arch Physiol Biochem. 2019;0:1–11. https://doi.org/10.1080/13813455.2019.1662454.
Caglar S, Altay A. In vitro anticancer activity of novel Co (II) and Ni (II) complexes of non-steroidal anti-inflammatory drug niflumic acid against human breast adenocarcinoma MCF-7 cells. Cell Biochem Biophys. 2021;79:729–46. https://doi.org/10.1007/s12013-021-00984-z.
Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell. 2002;9:459–70. https://doi.org/10.1016/S1097-2765(02)00482-3.
Garrido C, Galluzzi L, Brunet M, Puig PE, Didelot C. Mechanisms of cytochrome c release from mitochondria. Cell Death Differ. 2006;13:1423–33. https://doi.org/10.1038/sj.cdd.4401950.
Drew HR, Wing RM, Takano T, Broka C, Tanaka S, Itakura K, et al. Structure of a B-DNA dodecamer: conformation and dynamics. Proc Natl Acad Sci. 1981;78:2179–83. https://doi.org/10.1073/pnas.78.4.2179.
Feeney B, Pop C, Swartz P, Mattos C, Clark AC. Role of loop bundle hydrogen bonds in the maturation and activity of (Pro)caspase-3. Biochem-Us. 2006;45:13249–63. https://doi.org/10.1021/bi0611964.
Moradi SZ, Nowroozi A, Sadrjavadi K, Moradi S, Mansouri K, Hosseinzadeh L, et al. Direct evidences for the groove binding of the Clomifene to double stranded DNA. Int J Biol Macromol. 2018;114:40–53. https://doi.org/10.1016/j.ijbiomac.2018.03.040.
Arif A, Ahmad A, Ahmad M. Toxicity assessment of carmine and its interaction with calf thymus DNA. J Biomol Struct Dyn. 2021;39:5861. https://doi.org/10.1080/07391102.2020.1794962.
Laskowski RA, Swindells MB. LigPlot+: multiple ligand–protein interaction diagrams for drug discovery. J Chem Inf Model. 2011;51:2778–86. https://doi.org/10.1021/ci200227u.
Li JN, Abel R, Zhu K, Cao YX, Zhao SW, Friesner RA. The VSGB 2.0 model: a next generation energy model for high resolution protein structure modeling. Proteins. 2011;79:2794–812. https://doi.org/10.1002/prot.23106.
Anil DA, Aydin BO, Demir Y, Turkmenoglu B. Design, synthesis, biological evaluation and molecular docking studies of novel 1H-1, 2, 3-Triazole derivatives as potent inhibitors of carbonic anhydrase, acetylcholinesterase and aldose reductase. J Mol Struct. 2022;1257:132613. https://doi.org/10.1016/j.molstruc.2022.132613.
Schrödinger S. Release 2021-2: LigPrep, LLC, New York, NY; 2021.
Schrödinger S. Release 2021-2: Prime, LLC, New York, NY; 2021.
Schrödinger S. Release 2021-2: Glide, LLC, New York, NY; 2021.
Schrödinger S. Release 2021-2: Protein Preparation Wizard; Epik, LLC, New York, NY, 2021; Impact, Schrödinger, LLC, New York, NY; Prime, Schrödinger, LLC, New York, NY; 2021.