دورية أكاديمية
أعرض في EDS

Design and synthesis of novel cytotoxic fluoroquinolone analogs through topoisomerase inhibition, cell cycle arrest, and apoptosis.

التفاصيل البيبلوغرافية
العنوان: Design and synthesis of novel cytotoxic fluoroquinolone analogs through topoisomerase inhibition, cell cycle arrest, and apoptosis.
المؤلفون: Elanany MA; Department of Pharmaceutical Chemistry, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt. mohamed.elanany@buc.edu.eg., Osman EEA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Gedawy EM; Department of Pharmaceutical Chemistry, School of Pharmacy and Pharmaceutical Industries, Badr University in Cairo (BUC), Badr City, 11829, Cairo, Egypt.; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt., Abou-Seri SM; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt. sahar.shaarawy@pharma.cu.edu.eg.
المصدر: Scientific reports [Sci Rep] 2023 Mar 13; Vol. 13 (1), pp. 4144. Date of Electronic Publication: 2023 Mar 13.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Fluoroquinolones*/pharmacology , Antineoplastic Agents*/chemistry, Humans ; Molecular Structure ; Structure-Activity Relationship ; Moxifloxacin/pharmacology ; Cell Proliferation ; Cell Cycle Checkpoints ; Cell Line, Tumor ; Ciprofloxacin/pharmacology ; Apoptosis ; Ofloxacin/pharmacology ; Drug Screening Assays, Antitumor ; Cell Cycle
مستخلص: To exploit the advantageous properties of approved drugs to hasten anticancer drug discovery, we designed and synthesized a series of fluoroquinolone (FQ) analogs via functionalization of the acid hydrazides of moxifloxacin, ofloxacin, and ciprofloxacin. Under the NCI-60 Human Tumor Cell Line Screening Assay, (IIIf) was the most potent among moxifloxacin derivatives, whereas (VIb) was the only ofloxacin derivative with significant effects and ciprofloxacin derivatives were devoid of activity. (IIIf) and (VIb) were further selected for five-dose evaluation, where they showed potent growth inhibition with a mean GI 50 of 1.78 and 1.45 µM, respectively. (VIb) elicited a more potent effect reaching sub-micromolar level on many cell lines, including MDA-MB-468 and MCF-7 breast cancer cell lines (GI 50  = 0.41 and 0.42 µM, respectively), NSCLC cell line HOP-92 (GI 50  = 0.50 µM) and CNS cell lines SNB-19 and U-251 (GI 50  = 0.51 and 0.61 µM, respectively). (IIIf) and (VIb) arrested MCF-7 cells at G1/S and G1, respectively, and induced apoptosis mainly through the intrinsic pathway as shown by the increased ratio of Bax/Bcl-2 and caspase-9 with a lesser activation of the extrinsic pathway through caspase-8. Both compounds inhibited topoisomerase (Topo) with preferential activity on type II over type I and (VIb) was marginally more potent than (IIIf). Docking study suggests that (IIIf) and (VIb) bind differently to Topo II compared to etoposide. (IIIf) and (VIb) possess high potential for oral absorption, low CNS permeability and low binding to plasma proteins as suggested by in silico ADME calculations. Collectively, (IIIf) and (VIb) represent excellent lead molecules for the development of cytotoxic agents from quinolone scaffolds.
(© 2023. The Author(s).)
References: Anticancer Drugs. 2022 Jan 1;33(1):e235-e246. (PMID: 34419964)
J Natl Cancer Inst. 1991 Jun 5;83(11):757-66. (PMID: 2041050)
Nat Rev Cancer. 2002 Mar;2(3):188-200. (PMID: 11990855)
J Cell Biol. 1976 Oct;71(1):172-81. (PMID: 61966)
Toxicol In Vitro. 2019 Mar;55:75-92. (PMID: 30528372)
Apoptosis. 2014 Jan;19(1):269-84. (PMID: 24220853)
Nat Rev Cancer. 2006 Oct;6(10):813-23. (PMID: 16990858)
Nat Commun. 2021 May 20;12(1):2962. (PMID: 34016969)
Nat Med. 1997 Jun;3(6):614-20. (PMID: 9176486)
Anal Biochem. 1981 Apr;112(2):195-203. (PMID: 6266278)
J Thorac Oncol. 2012 Apr;7(4):731-6. (PMID: 22425922)
Q Rev Biophys. 1998 May;31(2):107-44. (PMID: 9794033)
Eur J Med Chem. 2017 Oct 20;139:250-262. (PMID: 28802125)
Biochem Biophys Res Commun. 2016 Mar 18;471(4):639-45. (PMID: 26902121)
Curr Med Chem Anticancer Agents. 2005 Jul;5(4):363-72. (PMID: 16101488)
Dev Biol Stand. 1998;93:119-23. (PMID: 9737386)
Drugs Aging. 1997 Jun;10(6):473-85. (PMID: 9205852)
Clin Infect Dis. 1996 Dec;23 Suppl 1:S19-24. (PMID: 8953102)
J Photochem Photobiol B. 2018 Dec;189:104-118. (PMID: 30339990)
J Enzyme Inhib Med Chem. 2020 Dec;35(1):1781-1799. (PMID: 32975138)
Cancer Cell Int. 2013 Jul 02;13(1):67. (PMID: 23819802)
Curr Opin Investig Drugs. 2003 Dec;4(12):1455-9. (PMID: 14763132)
J Clin Oncol. 1999 Sep;17(9):2941-53. (PMID: 10561374)
J Med Chem. 2002 Dec 5;45(25):5564-75. (PMID: 12459024)
Curr Opin Genet Dev. 2014 Apr;25:15-21. (PMID: 24584092)
CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
CA Cancer J Clin. 2020 Jan;70(1):7-30. (PMID: 31912902)
Oncogene. 2006 Aug 7;25(34):4798-811. (PMID: 16892092)
BMC Cancer. 2015 Aug 11;15:581. (PMID: 26260159)
J Immunol Methods. 1983 Dec 16;65(1-2):55-63. (PMID: 6606682)
Drugs. 1999;58 Suppl 2:29-36. (PMID: 10553702)
Drugs. 1998 Oct;56(4):709-23. (PMID: 9806112)
Gynecol Oncol. 2021 May;161(2):573-580. (PMID: 33551200)
Expert Opin Investig Drugs. 2012 Aug;21(8):1223-33. (PMID: 22724917)
J Cell Biol. 1975 Jul;66(1):188-93. (PMID: 49354)
Breast Cancer Res Treat. 2009 Sep;117(1):219-21. (PMID: 18853248)
Methods Mol Biol. 2011;731:237-45. (PMID: 21516412)
Arch Pharm (Weinheim). 2019 Jul;352(7):e1800376. (PMID: 31215674)
Mini Rev Med Chem. 2005 Nov;5(11):1009-17. (PMID: 16307530)
Cytometry. 1999 Nov 1;37(3):197-204. (PMID: 10520200)
Int J Oncol. 2018 May;52(5):1727-1737. (PMID: 29532860)
Acta Pharmacol Sin. 2012 Feb;33(2):271-8. (PMID: 22301863)
Am J Med. 1991 Dec 30;91(6A):45S-50S. (PMID: 1767806)
Clin Pharm. 1988 Aug;7(8):574-81. (PMID: 3048848)
J Natl Cancer Inst. 1990 Jul 4;82(13):1107-12. (PMID: 2359136)
Biochemistry. 2012 Feb 28;51(8):1730-9. (PMID: 22304499)
Drugs. 1999 Mar;57(3):363-73; discussion 374. (PMID: 10193688)
J Mol Graph Model. 2002 Jan;20(4):297-303. (PMID: 11858638)
Neurology. 2003 Nov 25;61(10):1332-8. (PMID: 14638950)
Oncogene. 2001 Oct 4;20(45):6570-8. (PMID: 11641782)
Drugs. 1999 Sep;58(3):533-51. (PMID: 10493279)
Bioorg Med Chem. 2016 Apr 15;24(8):1898-908. (PMID: 26988802)
J Biochem Mol Toxicol. 2021 Feb;35(2):e22638. (PMID: 33002289)
Methods Mol Med. 2004;88:191-202. (PMID: 14634230)
J Photochem Photobiol B. 2020 Jan;203:111733. (PMID: 31887636)
المشرفين على المادة: 0 (Fluoroquinolones)
U188XYD42P (Moxifloxacin)
0 (Antineoplastic Agents)
5E8K9I0O4U (Ciprofloxacin)
A4P49JAZ9H (Ofloxacin)
تواريخ الأحداث: Date Created: 20230314 Date Completed: 20230315 Latest Revision: 20230418
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC10011602
DOI: 10.1038/s41598-023-30885-5
PMID: 36914702
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-023-30885-5