دورية أكاديمية
أعرض في EDS

Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4- d ]pyrimidine derivatives.

التفاصيل البيبلوغرافية
العنوان: Design, synthesis, pharmacological evaluation, and in silico studies of the activity of novel spiro pyrrolo[3,4- d ]pyrimidine derivatives.
المؤلفون: Alzahrani AYA; Department of Chemistry, Faculty of Science and Arts, King Khalid University Mohail Assir Saudi Arabia ayalzahrani@kku.edu.sa., Shehab WS; Department of Chemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt dr.wesamshehab@gmail.com wsshehab@zu.edu.eg., Amer AH; Department of Chemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt dr.wesamshehab@gmail.com wsshehab@zu.edu.eg., Assy MG; Department of Chemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt dr.wesamshehab@gmail.com wsshehab@zu.edu.eg., Mouneir SM; Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University Cairo 12211 Egypt., Aziz MA; Department of Chemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt dr.wesamshehab@gmail.com wsshehab@zu.edu.eg., Abdel Hamid AM; Department of Chemistry, Faculty of Science, Zagazig University Zagazig 44519 Egypt dr.wesamshehab@gmail.com wsshehab@zu.edu.eg.
المصدر: RSC advances [RSC Adv] 2024 Jan 02; Vol. 14 (2), pp. 995-1008. Date of Electronic Publication: 2024 Jan 02 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101581657 Publication Model: eCollection Cited Medium: Internet ISSN: 2046-2069 (Electronic) Linking ISSN: 20462069 NLM ISO Abbreviation: RSC Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Cambridge [England] : Royal Society of Chemistry, [2011]-
مستخلص: In the present study, spiro compounds are shown to have distinctive characteristics because of their interesting conformations and their structural impacts on biological systems. A new family of functionalized spiro pyrrolo[3,4- d ]pyrimidines is prepared via the one-pot condensation reaction of amino cyclohexane derivatives with benzaldehyde to prepare fused azaspiroundecanedione and azaspirodecenone/thione derivatives. A series of synthesized spiro compounds were scanned against DPPH and evaluated for their ability to inhibit COX-1 and COX-2. All compounds exhibit significant antiinflammatory activity, and they inhibited both COX-1 and COX-2 enzymes with a selectivity index higher than celecoxib as a reference drug. The most powerful and selective COX-2 inhibitor compounds were 11 and 6, with selectivity indices of 175 and 129.21 in comparison to 31.52 of the standard celecoxib. However, candidate 14 showed a very promising antiinflammatory activity with an IC 50 of 6.00, while celecoxib had an IC 50 of 14.50. Our findings are promising in the area of medicinal chemistry for further optimization of the newly designed and synthesized compounds regarding the discussed structure-activity relationship study (SAR), in order to obtain a superior antioxidant lead compound in the near future. All chemical structures of the novel synthesized candidates were unequivocally elucidated and confirmed utilizing spectroscopic and elemental investigations.
Competing Interests: The authors declare that they have no conflicts of interest.
(This journal is © The Royal Society of Chemistry.)
References: Expert Opin Investig Drugs. 2013 Dec;22(12):1671-86. (PMID: 24070205)
Eur J Med Chem. 2011 May;46(5):1926-34. (PMID: 21397368)
Int J Mol Sci. 2021 Sep 27;22(19):. (PMID: 34638734)
Chem Biol Drug Des. 2015 Mar;85(3):377-84. (PMID: 25130070)
ACS Chem Neurosci. 2012 Sep 19;3(9):649-57. (PMID: 23019491)
Chem Biol Drug Des. 2021 Aug;98(2):270-282. (PMID: 34021971)
Pharmaceutics. 2019 Feb 17;11(2):. (PMID: 30781584)
Int J Mol Sci. 2020 Dec 18;21(24):. (PMID: 33353225)
Eur J Med Chem. 2005 Sep;40(9):862-74. (PMID: 15908051)
Chem Cent J. 2018 Apr 4;12(1):38. (PMID: 29619583)
Arzneimittelforschung. 2009;59(12):666-71. (PMID: 20108654)
Molecules. 2015 Jul 13;20(7):12670-85. (PMID: 26184146)
Anticancer Agents Med Chem. 2020;20(18):2150-2168. (PMID: 32628593)
Org Biomol Chem. 2020 Feb 7;18(5):810-829. (PMID: 31942901)
J Biochem Mol Toxicol. 2018 Feb;32(2):. (PMID: 29243863)
Chem Asian J. 2009 Jan 5;4(1):32-41. (PMID: 18770872)
Int J Mol Sci. 2022 Aug 09;23(16):. (PMID: 36012121)
Am J Pathol. 2000 Jul;157(1):145-58. (PMID: 10880385)
Med Chem. 2014;10(5):521-32. (PMID: 24151878)
Eur J Med Chem. 2007 Feb;42(2):146-51. (PMID: 17011080)
Antioxidants (Basel). 2022 Jul 26;11(8):. (PMID: 35892646)
Molecules. 2017 Sep 09;22(9):. (PMID: 28891941)
Molecules. 2022 Mar 23;27(7):. (PMID: 35408463)
Molecules. 2019 Jul 23;24(14):. (PMID: 31340431)
Chem Biol Drug Des. 2019 May;93(5):657-665. (PMID: 30721578)
J Comput Aided Mol Des. 2015 Feb;29(2):101-12. (PMID: 25428568)
J Med Chem. 1995 Dec 8;38(25):4950-2. (PMID: 8523409)
Sci Rep. 2022 Jan 10;12(1):381. (PMID: 35013389)
Prostaglandins. 1983 Apr;25(4):531-40. (PMID: 6410459)
Arch Pharm (Weinheim). 2020 Sep;353(9):e2000084. (PMID: 32583459)
Bioorg Chem. 2021 Sep;114:105136. (PMID: 34328860)
Bioorg Chem. 2021 Sep;114:105076. (PMID: 34157555)
Arch Pharm (Weinheim). 2006 May;339(5):255-61. (PMID: 16511896)
Molecules. 2021 Jun 27;26(13):. (PMID: 34198975)
J Enzyme Inhib Med Chem. 2018 Dec;33(1):583-606. (PMID: 29529892)
Molecules. 2022 Jan 25;27(3):. (PMID: 35164032)
Redox Rep. 2022 Dec;27(1):92-99. (PMID: 35435141)
J Enzyme Inhib Med Chem. 2013 Aug;28(4):830-5. (PMID: 22651798)
Eur J Med Chem. 2005 Jul;40(7):694-700. (PMID: 15935904)
Biochim Biophys Acta Mol Cell Res. 2021 Jan;1868(1):118896. (PMID: 33096143)
Bioorg Chem. 2023 Feb;131:106280. (PMID: 36436418)
Free Radic Biol Med. 1996;20(5):707-27. (PMID: 8721615)
Methods Mol Biol. 2008;443:365-82. (PMID: 18446297)
Chemistry. 2016 Feb 24;22(9):2856-81. (PMID: 26661053)
Pharmacol Res Perspect. 2018 Nov 08;6(6):e00438. (PMID: 30455959)
Int J Med Chem. 2014;2014:202784. (PMID: 25383216)
Bioorg Med Chem. 2011 Jul 15;19(14):4295-306. (PMID: 21696965)
Eur J Med Chem. 2018 Oct 5;158:917-936. (PMID: 30261467)
Int J Med Chem. 2014;2014:761030. (PMID: 25383223)
Int J Mol Sci. 2022 Sep 15;23(18):. (PMID: 36142688)
J Org Chem. 2008 Sep 5;73(17):6623-35. (PMID: 18662034)
ACS Omega. 2020 Jun 15;5(24):14635-14644. (PMID: 32596601)
Mini Rev Med Chem. 2021;21(3):362-379. (PMID: 32912125)
J Med Chem. 1995 Sep 29;38(20):3895-901. (PMID: 7562922)
تواريخ الأحداث: Date Created: 20240104 Latest Revision: 20240105
رمز التحديث: 20240105
مُعرف محوري في PubMed: PMC10759174
DOI: 10.1039/d3ra07078f
PMID: 38174254
قاعدة البيانات: MEDLINE
الوصف
تدمد:2046-2069
DOI:10.1039/d3ra07078f