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Research Article

Synthesis, in vitro and in silico anticancer evaluation of novel pyridin-2-yl estra-1,3,5(10)-triene derivatives

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Received 01 Feb 2024, Accepted 26 Mar 2024, Published online: 17 Apr 2024

References

  • Ahmad N, Kumar R. Steroid hormone receptors in cancer development: a target for cancer therapeutics. Cancer Lett. 2011;300:1–9. doi: 10.1016/j.canlet.2010.09.00
  • Tantawy MA, Nafie MS, Elmegeed GA et al. Auspicious role of the steroidal heterocyclic derivatives as a platform for anti-cancer drugs. Bioorg Chem. 2017;73:128–146. doi: 10.1016/j.bioorg.2017.06.006
  • Ibrahim-Ouali M, Dumur F. Recent syntheses of steroidal derivatives containing heterocycles. Arkivoc 2019;1:304–339. doi: 10.24820/ark.5550190.p010.988
  • Martins P, Jesus J, Santos S et al. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine's tool box. Molecules 2015;20:16852–16891. doi: 10.3390/molecules200916852
  • Singh R, Panda G. An overview of synthetic approaches for heterocyclic steroids. Tetrahedron 2013;69:2853–2884. doi: 10.1016/j.tet.2013.02.018
  • Gomtsyan A. Heterocycles in drugs and drug discovery. Chem Heterocycl. 2012;48:7–10. doi: 10.1007/s10593-012-0960-z
  • Lone IH, Khan KZ, Fozdar BI et al. Synthesis antimicrobial and antioxidant studies of new oximes of steroidal chalcones. Steroids 2013;78:945–950. doi: 10.1016/j.steroids.2013.05.01
  • Salem MS, Sakr SI, El-Senousy WM et al. Synthesis, antibacterial, and antiviral evaluation of new heterocycles containing the pyridine moiety. Archiv. Der. Pharmazie. 2013;346:766–773. doi: 10.1002/ardp.201300183
  • Karegoudar P, Karthikeyan MS, Prasad DJ et al. Synthesis of some novel 2,4-disubstituted thiazoles as possible antimicrobial agents. Eur. J. Med. Chem. 2008;43:261–267. doi: 10.1016/j.ejmech.2007.03.014
  • Abd El-Galil Ea A, Abdullab MM. Synthesis and pharmacological screening of some new pyrimidine and cyclohexenone fused steroidal derivatives. Indian J. Heterocycl. Chem. 2002;12:129–134.
  • Dubey R. Sex hormones and hypertension. Cardiovasc. Res. 2002;53:688–708. doi: 10.1016/s0008-6363(01)00527-2
  • Jarman M, Barrie SE, Llera JM. The 16,17-double bond is needed for irreversible inhibition of human cytochrome P45017α by abiraterone (17-(3-Pyridyl)androsta-5,16-dien-3β-ol) and related steroidal inhibitors. J. Med. Chem. 1998;41:5375–5381. doi: 10.1021/jm981017j
  • Zhang W. Inhibition of cytochromes P450 by antifungal imidazole derivatives. Drug Metab. Dispos. 2002;30:314–318. doi: 10.1124/dmd.30.3.314
  • Kovács D, Mótyán G, Wölfling J et al. A facile access to novel steroidal 17-2′-(1′,3′,4′)-oxadiazoles, and an evaluation of their cytotoxic activities in vitro. Bioorg. Med. Chem. Lett. 2014;24:1265–1268. doi: 10.1016/j.bmcl.2014.01.069
  • Abdelhalim MM, Kamel EM, Rabie ST et al. Synthesis and biological evaluation of some nitrogen containing steroidal heterocycles. Steroids 2011;76:78–84. doi: 10.1016/j.steroids.2010.09.001
  • Monier M, El-Mekabaty A, Abdel-Latif D et al. Heterocyclic steroids: efficient routes for annulation of pentacyclic steroidal pyrimidines. Steroids 2019;154:108–548. doi: 10.1016/j.steroids.2019.108548
  • Cui J, Liu L, Zhao D et al. Synthesis, characterization and antitumor activities of some steroidal derivatives with side chain of 17-hydrazone aromatic heterocycle. Steroids 2015;95:32–38. doi: 10.1016/j.steroids.2015.01.002
  • Gupta A, Kumar BS, Negi AS. Current status on development of steroids as anticancer agents. J. Steroid Biochem. Mol. Biol. 2013;137:242–270. doi: 10.1016/j.jsbmb.2013.05.011
  • Almeida CF, Oliveira A, Ramos MJ et al. Estrogen receptor-positive (ER+) breast cancer treatment: are multi-target compounds the next promising approach? Biochem. Pharmacol. 2020;177:113989. doi: 10.1016/j.bcp.2020.113989
  • Chumsri S. Clinical utilities of aromatase inhibitors in breast cancer. Int. J. Womens Health 2015;7:493–499. doi: 10.2147/IJWH.S69907
  • Penning TM, Jonnalagadda S, Trippier PC et al. Aldo-keto reductases and cancer drug resistance. Pharmacol. Rev. 2021;73:1150–1171. doi: 10.1124/pharmrev.120.000122
  • Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep. 2017;7:1–13. doi: 10.1038/srep42717
  • Lipinski C, Lombardo F, Dominy B et al. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 2001;46:3–26. doi: 10.1016/S0169-409X(00)00129-0
  • Ghose AK, Viswanadhan VN, Wendoloski JJ. A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. a qualitative and quantitative characterization of known drug databases. J. Comb. Chem. 1999;1:55–68. doi: 10.1021/cc9800071
  • Veber D, Johnson S, Cheng H-Y et al. Molecular properties that influence the oral bioavailability of drug candidates. J. Med. Chem. 2002;45:2615–2623. doi: 10.1021/jm020017n
  • Egan WJ, Merz KM, Baldwin JJ. Prediction of drug absorption using multivariate statistics. J. Med. Chem. 2000;43:3867–3877. doi: 10.1021/jm000292e
  • Muegge I, Heald SL, Brittelli D. Simple selection criteria for drug-like chemical matter. J. Med. Chem. 2001;44:1841–1846. doi: 10.1021/jm015507e
  • Bhutania R, Pal Pathak D, Kapoor G et al. Novel hybrids of benzothiazole-1,3,4-oxadiazole-4-thiazolidinone: synthesis, in silico ADME study, molecular docking and in vivo anti-diabetic assessment. Bioorg. Chem. 2019;83:6–19. doi: 10.1016/j.bioorg.2018.10.025
  • Zhao YH, Abraham MH, Le J et al. Rate-limited steps of human oral absorption and QSAR studies. Pharm. Res. 2002;19:1446–1457. doi: 10.1023/A:1020444330011
  • Kuzminac I, Klisurić OR, Škorić D et al. Structural analysis and antitumor potential of novel 5,6-disubstituted-17a-homo-17-oxa-androstane derivatives. Struct. Chem. 2017;28:567–576. doi: 10.1007/s11224-016-0815-9
  • Bekić SS, Marinović MA, Petri ET et al. Identification of D-seco modified steroid derivatives with affinity for estrogen receptor α and β isoforms using a non-transcriptional fluorescent cell assay in yeast. Steroids 2018;130:22–30. doi: 10.1016/j.steroids.2017.12.002
  • Savić MP, Ajduković JJ, Plavša JJ et al. Evaluation of A-ring fused pyridine D-modified androstane derivatives for antiproliferative and aldo-keto reductase 1C3 inhibitory activity. MedChemComm. 2018;9:969–981. doi: 10.1039/C8MD00077H
  • Kuzminac IZ, Jakimov DS, Bekić SS et al. Synthesis and anticancer potential of novel 5, 6-oxygenated and/or halogenated steroidal D-homo lactones. Bioorg. Med. Chem. 2021;30:115935. doi: 10.1016/j.bmc.2020.115935
  • Muddana SS, Peterson BR. Fluorescent cellular sensors of steroid receptor ligands. ChemBioChem 2003;4:848–855. doi: 10.1002/cbic.200300606
  • Gietz D, St Jean A, Woods RA et al. Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res. 1992;20:1425. doi: 10.1093/nar/20.6.1425
  • Brožič P, Golob B, Gomboc N et al. Cinnamic acids as new inhibitors of 17β-hydroxysteroid dehydrogenase type 5 (AKR1C3). Mol. Cell Endocrinol. 2006;248:233–235. doi: 10.1016/j.mce.2005.10.020
  • Davies NJ, Hayden RE, Simpson PJ et al. AKR1C isoforms represent a novel cellular target for jasmonates alongside their mitochondrial-mediated effects. Cancer Res. 2009;69:4769–4775. doi: 10.1158/0008-5472.CAN-08-4533
  • Kruger NJ. The Bradford Method For Protein Quantitation. In: Walker JM editor. The Protein Protocols Handbook. Springer Protocols Handbooks. NJ, USA: Humana Press; 2009. p. 17–24. doi: 10.1007/978-1-59745-198-7_4
  • Drury JE, Di Costanzo L, Penning TM et al. Inhibition of human steroid 5β-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex. J. Biol. Chem. 2009;284:19786–19790. doi: 10.1074/jbc.C109.016931
  • Heer J, Hoffmann K. Über Pyridyl-Steroide. II. Über Steroide, 142. Mitteilung. Helv. Chim. Acta 1956;39:1814–1820. doi: 10.1002/hlca.19560390641
  • Penov-Gaši KM, Djurendić MDJ, Djurendić EA et al. Synthesis and biological evaluation of some 17-picolyl and 17-picolinylidene androst-5-ene derivatives. Steroids 2007;27:31–40. doi: 10.1016/j.steroids.2006.10.002
  • Hoffmann K, Heer J. Binningen, inventors Switzerland, assignors to Ciba Pharmaceutical Products Inc., Summit, NJ. New steroids substitued by a heterocyclic nitrogen-containing ring in 17-position. United States patent US patent 2,938,030. 1960 May 24.
  • Stevanović M, Kuzminac I. Synthesis, structural characterization, and in silico ADMET testing of novel 17β-acetoxy-17α-(pyridin-2-yl) estrane derivatives. Poster session presented at: 8th International Electronic Conference on Medicinal Chemistry. MDPI: Basel, Switzerland 2022 November 1–30.
  • Daina A, Zoete V. A BOILED-egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem 2016;11:1117–1121. doi: 10.1002/cmdc.201600182
  • Brodie A, Njar V, Macedo LF et al. The Coffey Lecture: steroidogenic enzyme inhibitors and hormone dependent cancer. Urol. Oncol.: Semin. Orig. 2009;27:53–63. doi: 10.1016/j.urolonc.2008.07.036
  • Cremoux P, Diéras V, Poupon MF et al. Tamoxifen and aromatase inhibitors in the treatment of breast cancer in menopausal women: pharmacological and clinical aspects. Bull Cancer 2004;91:917–927.
  • Woo LL, Bubert C, Purohit A et al. Hybrid dual aromatase-steroid sulfatase inhibitors with exquisite picomolar inhibitory activity. ACS Med. Chem. Lett. 2011;2:243–247. doi: 10.1021/ml100273k
  • Martin-Yken H. Yeast-based biosensors: current applications and new developments. Biosensors 2020;10:51. doi: 10.3390/bios10050051
  • Ali S, Coombes RC. Estrogen receptor alpha in human breast cancer: occurrence and significance. J. Mammary Gland Biol. Neoplasia 2000;5:271–281. doi: 10.1023/A:1009594727358
  • Szelei J, Jimenez J, Soto AM et al. Sonnenschein C, Androgen-induced inhibition of proliferation in human breast cancer MCF7 cells transfected with androgen receptor. Endocrinology 1997;138:1406–1412. doi: 10.1210/endo.138.4.5047
  • Macedo LF, Guo Z, Tilghman SL et al. Role of androgens on MCF-7 breast cancer cell growth and on the inhibitory effect of letrozole. Cancer Res. 2006;66:7775–7782. doi: 10.1158/0008-5472.CAN-05-3984
  • Carruba G, Pfeffer U, Fecarotta E et al. Estradiol inhibits growth of hormone-nonresponsive PC3 human prostate cancer cells. Cancer Res. 1994;54:1190–1193. PMID: 8118804.
  • Piccolella M, Crippa V, Messi E et al. Modulators of estrogen receptor inhibit proliferation and migration of prostate cancer cells. Pharmacol. Res. 2014;79:13–20. doi: 10.1016/j.phrs.2013.10.002
  • Al-Bader M, Ford C, Al-Ayadhy B et al. Analysis of estrogen receptor isoforms and variants in breast cancer cell lines. Exp. Ther. Med. 2011;2:537–544. doi: 10.3892/etm.2011.226
  • Monje P, Boland R. Expression and cellular localization of naturally occurring β estrogen receptors in uterine and mammary cell lines. J. Cell Biochem. 2002;86:136–144. doi: 10.1002/jcb.10193
  • Baravalle R, Di Nardo G, Bandino A et al. Impact of R264C and R264H polymorphisms in human aromatase function. J. Steroid Biochem. Mol. Biol. 2017;167:23–32. doi: 10.1016/j.jsbmb.2016.09.022
  • Sevrioukova IF, Poulos TL. Current approaches for investigating and predicting cytochrome P450 3A4-ligand interactions. In: Hrycay E, Bandiera S eds. Monooxygenase, Peroxidase and Peroxygenase Properties and Mechanisms of Cytochrome P450. Springer, Cham: Advances in Experimental Medicine and Biology; 2015. p. 83–105. doi: 10.1007/978-3-319-16009-2_3
  • Ertas M, Sahin Z, Berk B et al. Pyridine-substituted thiazolylphenol derivatives: synthesis, modeling studies, aromatase inhibition, and antiproliferative activity evaluation. Arch Pharm. 2018;351:1700272. doi: 10.1002/ardp.201700272
  • Isin EM, Guengerich FP. Substrate binding to cytochromes P450. Anal. Bioanal. Chem. 2008;392:1019–1030. doi: 10.1007/s00216-008-2244-0
  • Di Nardo G, Breitner M, Sadeghi SJ et al. Dynamics and flexibility of human aromatase probed by FTIR and time resolved fluorescence spectroscopy. PLOS ONE 2013;8:e82118. doi: 10.1371/journal.pone.0082118
  • Conner KP, Cruce AA, Krzyaniak MD et al. Drug modulation of water-heme interactions in low-spin P450 complexes of CYP2C9d and CYP125A1. Biochemistry 2015;54:1198–1207. doi: 10.1021/bi501402k
  • Liu C, Armstrong CM, Lou W et al. Inhibition of AKR1C3 activation overcomes resistance to abiraterone in advanced prostate cancer AKR1C3 confers resistance to abiraterone. Mol. Cancer Ther. 2017;16:35–44. doi: 10.1158/1535-7163.MCT-16-0186
  • Khanim F, Davies N, Veliça P et al. Selective AKR1C3 inhibitors do not recapitulate the anti-leukaemic activities of the pan-AKR1C inhibitor medroxyprogesterone acetate. Br. J. Cancer 2014;110:1506–1516. doi: 10.1038/bjc.2014.83
  • Marinović MA, Petri ET, Grbović LM et al. Investigation of the potential of bile acid methyl esters as inhibitors of aldo-keto reductase 1C2: insight from molecular docking, virtual screening, experimental assays and molecular dynamics. Mol Inform. 2022;41:2100256. doi: 10.1002/minf.202100256

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