Abstract

Review Article

Beta-1 Receptor (β1) in the Heart Specific Indicate to Stereoselectivity

Rezk Rezk Ayyad*, Ahmed Mohamed Mansour, Ahmed Mohamed Nejm, Yasser Abdel Allem Hassan, Norhan Hassan Gabr and Ahmed Rezk Ayyad

Published: 10 July, 2024 | Volume 8 - Issue 1 | Pages: 082-088

The β1 receptor is one of the three beta receptors present in the human body, namely β1, β2, and β3. The β1 receptor is predominantly located in the heart, where it plays a crucial role in regulating the heart rate and the force of contraction, thereby increasing the cardiac output and the efficiency of blood pumping throughout the body. This receptor is targeted by a variety of pharmaceutical agents known as beta-blockers, which are commonly used in the treatment of cardiovascular conditions such as hypertension, angina, and arrhythmias.
The β1 receptor exhibits stereoselectivity, meaning that different enantiomers (chiral molecules) of beta blockers can have varying levels of effectiveness and side effects. This study focuses on the stereoselectivity of the β1 receptor and the clinical implications of this property. It includes an examination of various β1 blockers, such as propranolol (a non-selective beta  blocker), and selective β1 blockers like atenolol, bisoprolol, nebivolol, metoprolol, esmolol, acebutolol, and betaxolol. Each of these drugs has a unique chemical structure, with specific functional groups that contribute to their selective action on the β1 receptor.
Furthermore, the β2 receptor, which is mainly present in the bronchi and bronchioles, is responsible for bronchodilation, and the β3 receptor, found in the bladder, helps reduce urinary urgency. Understanding the distinct locations and functions of these receptors allows for the development of targeted therapies with minimal off-target effects.
This review highlights the importance of stereoselectivity in the development and use of β1 blockers, discussing their chemical structures, pharmacological activities, and therapeutic uses. It also explores the potential for future research and development of more selective and effective β1 receptor agonists and antagonists, which could offer improved therapeutic outcomes for patients with cardiovascular diseases.
This study underscores the significant role of the β1 receptor in cardiovascular health and provides insights into the ongoing advancements in beta-blocker therapy. By delving into the stereoselectivity and specific actions of these drugs, the research aims to enhance the understanding and optimization of β1 receptor-targeted treatments in clinical practice.

Read Full Article HTML DOI: 10.29328/journal.apps.1001060 Cite this Article Read Full Article PDF

Keywords:

β1 Receptor, Beta Blockers, Stereoselectivity, Propranolol, Atenolol, Metoprolol

References

  1. Ayyad RR, Mansour AM, Nejm AM, Hassan YAA, Ayyad AR. Stereo Selectivity of Histaminic Receptors Plays an Important Role in Anti-histaminic Activity. Curr Res Med Sci. 2024;3(1):10-17. Available from: https://www.pioneerpublisher.com/crms/article/view/634
  2. Al-Warhi T, El Kerdawy AM, Aljaeed N, Ismael OE, Ayyad RR, Eldehna WM, et al. Synthesis, Biological Evaluation and In Silico Studies of Certain Oxindole-Indole Conjugates as Anticancer CDK Inhibitors. Molecules. 2020;25(9):2031. Available from: https://pubmed.ncbi.nlm.nih.gov/32349307/
  3. Ayyad RR, Nejm AM, Ayyad AR. The Isomers of Some Drugs One Effective and the Other Is Toxic or Ineffective. Curr Res Med Sci. 2023;2(2):58-62. Available from: https://www.pioneerpublisher.com/crms/article/view/317
  4. Alanazi AM, Abdel-Aziz AA, Shawer TZ, Ayyad RR, Al-Obaid AM, et al. Synthesis, antitumor and antimicrobial activity of some new 6-methyl-3-phenyl-4(3H)-quinazolinone analogues: in silico studies. J Enzyme Inhib Med Chem. 2016;31(5):721-35. Available from: https://pubmed.ncbi.nlm.nih.gov/26162029/
  5. El-Azab AS, Abdel-Aziz AA, Ayyad RR, Ceruso M, Supuran CT. Inhibition of carbonic anhydrase isoforms I, II, IV, VII and XII with carboxylates and sulfonamides incorporating phthalimide/phthalic anhydride scaffolds. Bioorg Med Chem. 2016;24(1):20-5. Available from: https://pubmed.ncbi.nlm.nih.gov/26678172/
  6. Ibrahim MK, Abd-Elrahman AA, Ayyad RRA, El-Adl K, Mansour AM, et al. Design and synthesis of some novel 2-(3-methyl-2-oxoquinoxalin-1 (2H)-yl)-N-(4-(substituted) phenyl) acetamide derivatives for biological evaluation as anticonvulsant agents. Bull Fac Pharm Cairo Univ. 2013;51(1):101-111. Available from: https://www.sciencedirect.com/science/article/pii/S1110093112000555
  7. Al Ward M, Abdallah AE, Zayed M, Ayyad R, El-Zahabi M. New immunomodulatory anticancer quinazolinone based thalidomide analogs: Design, synthesis and biological evaluation. 2023. Available from: https://assets-eu.researchsquare.com/files/rs-2916749/v1_covered_2c995cf5-39ef-46f0-a9b9-f0cb20f6d8c1.pdf?c=1686750506
  8. Mohamed MA, Ayyad RR, Shawer TZ, Abdel-Aziz AA, El-Azab AS. Synthesis and antitumor evaluation of trimethoxyanilides based on 4(3H)-quinazolinone scaffolds. Eur J Med Chem. 2016;112:106-113. Available from: https://pubmed.ncbi.nlm.nih.gov/26890117/
  9. Osman IA, Ayyad RR, Mahdy HA. New pyrimidine-5-carbonitrile derivatives as EGFR inhibitors with anticancer and apoptotic activities: design, molecular modeling and synthesis. New J Chem. 2022;46(24):11812-11827. Available from: https://pubs.rsc.org/en/content/articlelanding/2022/nj/d2nj01451c
  10. Mahdy H, Shaat M. Recent advances in drugs targeting protein kinases for cancer therapy. Al-Azhar J Pharm Sci. 2022;66(2):56-86. Available from: https://journals.ekb.eg/article_268384.html
  11. El-Adl K, El-Helby AA, Ayyad RR, Mahdy HA, Khalifa MM, Elnagar HA, et al. Design, synthesis, and anti-proliferative evaluation of new quinazolin-4(3H)-ones as potential VEGFR-2 inhibitors. Bioorg Med Chem. 2021;29:115872. Available from: https://pubmed.ncbi.nlm.nih.gov/33214036/.
  12. Nassar E, El-Badry YA, Eltoukhy AMM, Ayyad RR. Synthesis and Antiproliferative Activity of 1-(4-(1H-Indol-3-Yl)-6-(4-Methoxyphenyl) Pyrimidin-2-yl) Hydrazine and Its Pyrazolo Pyrimidine Derivatives. Med Chem (Los Angeles). 2016;6:224-233. Available from: https://www.hilarispublisher.com/open-access/synthesis-and-antiproliferative-activity-of-141hindol3yl64methoxyphenylpyrimidin2ylhydrazine-and-its-pyrazolo-pyrimidine-derivativ-2161-0444-1000350.pdf
  13. Ayyad RR, Nejm AM, Elbahat ELT, Elnagar AM, Aljazar MA. The Configuration of Some Hormonal Compounds Play an Important Role in Pharmacological Action (Agonist, Antagonist, Active, More Active). 2023;2(3):23-29. Available from: https://www.pioneerpublisher.com/jpeps/article/view/418
  14. Ibrahim A, Sakr HM, Ayyad RR, Khalifa MM. Design, Synthesis, In‐Vivo Anti‐Diabetic Activity, In‐Vitro α‐Glucosidase Inhibitory Activity and Molecular Docking Studies of Some Quinazolinone Derivatives. ChemistrySelect. 2022;7(14). Available from: https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/slct.202104590
  15. Sakr HM, Ayyad RR, Mahmoud K, Mansour AM, Ahmed G. Design, Synthesis of Analgesics and Anticancer of Some New Derivatives of Benzimidazole. Int J Org Chem. 2021;11(03):144-169. Available from: https://www.scirp.org/journal/paperinformation?paperid=112320
  16. Ayyad RR. Synthesis and Biological Evaluation of Novel Iodophthalazinedione Derivatives as Anticonvulsant Agents. Al-Azhar J Pharm Sci. 2012;45(1):1-13. Available from: https://ajps.journals.ekb.eg/article_7146.html
  17. Al-Warhi T, Almahli H, Maklad RM, Elsayed ZM, El Hassab MA, Alotaibi OJ, et al. 1-Benzyl-5-bromo-3-hydrazonoindolin-2-ones as Novel Anticancer Agents: Synthesis, Biological Evaluation and Molecular Modeling Insights. Molecules. 2023;28(7):3203. Available from: https://pubmed.ncbi.nlm.nih.gov/37049966/
  18. Salem M, Ayyad R, Sakr H. Design and Synthesis of Some New Oxadiazole Derivatives as Anticancer Agents. Int J Org Chem. 2022;12(02):64-74. Available from: https://www.scirp.org/journal/paperinformation?paperid=117052
  19. Ayyad R, Sakr H, Gaafer A. Design and Synthesis of New Compounds Derived from Phenyl Hydrazine and Different Aldehydes as Anticancer Agents. Int J Org Chem. 2022;12(1):28-39. Available from: https://www.scirp.org/journal/paperinformation?paperid=116252
  20. Ayyad RA, Sakr HM, El-Gamal KM. Design, Synthesis, Computer Modeling and Analgesic Activity of Some New Disubstituted Quinazolin-4(3H)-ones. Med Chem. 2016;6(5):299-305. Available from: https://www.hilarispublisher.com/open-access/design-synthesis-computer-modeling-and-analgesic-activity-of-some-newdisubstituted-quinazolin43hones-2161-0444-1000360.pdf
  21. Ayyad R. Synthesis and Anticonvulsant Activity of 6-Iodo Phthalazinedione Derivatives. Al-Azhar J Pharm Sci. 2014;50(2):43-54. Available from: https://ajps.journals.ekb.eg/article_6930.html
  22. Abdel-Aziz AA, El-Azab AS, Alanazi AM, Asiri YA, Al-Suwaidan IA, Maarouf AR, et al. Synthesis and potential antitumor activity of 7-(4-substituted piperazin-1-yl)-4-oxoquinolines based on ciprofloxacin and norfloxacin scaffolds: in silico studies. J Enzyme Inhib Med Chem. 2016;31(5):796-809. Available from: https://pubmed.ncbi.nlm.nih.gov/26226179/
  23. Khalifa MM, Sakr HM, Ibrahim A, Mansour AM, Ayyad RR. Design and synthesis of new benzylidene-quinazolinone hybrids as potential anti-diabetic agents: In vitro α-glucosidase inhibition, and docking studies. J Mol Struct. 2022;1250:131768. Available from: https://www.scirp.org/reference/referencespapers?referenceid=3205061
  24. Ibrahim MK, El-Helby AEA, Ghiaty AH, Biomy AH, Abd-El Rahman AA. Modeling, synthesis and antihyperglycemic activity of novel quinazolinones containing sulfonylurea. 2009;7. Available from: https://d1wqtxts1xzle7.cloudfront.net/52726405/Modeling_Synthesis_and_Antihyperglycemic20170420-23469-3pjbru-libre.pdf?1492732308=&response-content-disposition=inline%3B+filename%3DModeling_Synthesis_and_Antihyperglycemic.pdf&Expires=1720587812&Signature=Eesy4nCT18iIb1sXIbwIDzN6JUb2SwzZRX560TBRvBfccFMef82Iq5oYZnhX70qFoBIOfBeb8fcmcdoFdSgwReIvyuDWSmN4kRNJLEaTKlaO-8BfM4JVUCVg8Yupg2LFclJ3Agd4bQjdVY6Q6faK3SZe06mVXDfbnDK834i6N67JZwxU2Ar9E7CmqDP9Dvrwxfkx~~fykomeM-WoJdPBSZNWMcdwz5aBYuiF6zwfVAdO~srvzi~bg172Cr7cwLYO08zrvdqdwTXAePXP-oa5vpzLJzP3ObrC2GmRv3UoxclVdp7O5YE~POGodm1HGEoJ-eoMKrL3Aw71AoH-NGZAbw__&Key-Pair-Id=APKAJLOHF5GGSLRBV4ZA
  25. Al Ward MMS, Abdallah AE, Zayed MF, Ayyad RR, El-Zahabi MA. Design, synthesis and biological evaluation of newly triazolo-quinoxaline based potential immunomodulatory anticancer molecules. J Mol Struct. 2024;1298:137041. Available from: https://ui.adsabs.harvard.edu/abs/2024JMoSt129837041W/abstract
  26. Al-Suwaidan IA, Abdel-Aziz AA, Shawer TZ, Ayyad RR, Alanazi AM, El-Morsy AM, Mohamed MA, Abdel-Aziz NI, El-Sayed MA, El-Azab AS. Synthesis, antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues. J Enzyme Inhib Med Chem. 2016;31(1):78-89. Available from: https://pubmed.ncbi.nlm.nih.gov/25815668/
  27. Ayyad RR, Nejm AM, Ayyad AR. The Activity of Some Antibiotics Depend on Stereochemistry of Them (Its Structure). J Prog Eng Phys Sci. 2023;2(2):5-7. Available from: https://www.pioneerpublisher.com/jpeps/article/view/230
  28. El-Helby AGA, Ayyad RR, Sakr HM, Abdelrahim AS, El-Adl K, Sherbiny FS, et al. Design, synthesis, molecular modeling, and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents. J Mol Struct. 2017;1130:333-351. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0022286016310936
  29. Ayyad RR, Nejm AM, Abdelaleem YH, Ayyad AR. Hydrophobicity, Transport and Target Sites of Action Are Important for the Activity of Many Drugs. Curr Res Med Sci. 2023;2(3):15-19. Available from: https://www.pioneerpublisher.com/crms/article/view/375
  30. Sakr H, Ayyad RR, El-Helby AA, Khalifa MM, Mahdy HA. Discovery of novel triazolophthalazine derivatives as DNA intercalators and topoisomerase II inhibitors. Arch Pharm (Weinheim). 2021;354(6):e2000456. Available from: https://pubmed.ncbi.nlm.nih.gov/33554352/
  31. Eissa IH, Metwaly AM, Belal A, Mehany ABM, Ayyad RR, El-Adl K, et al. Discovery and antiproliferative evaluation of new quinoxalines as potential DNA intercalators and topoisomerase II inhibitors. Arch Pharm (Weinheim). 2019;352(11):e1900123. Available from: https://pubmed.ncbi.nlm.nih.gov/31463953/
  32. Ayyad RR, Nejm AM, Hassan YAA, Ayyad AR. The Lipid Solubility of Most Drugs Play Important Role of Its Pharmacological Action and Duration of Action. J Prog Eng Phys Sci. 2023;2(4):1-6. Available from: https://www.pioneerpublisher.com/jpeps/article/view/486
  33. El-Helby AA, Ayyad RRA, Zayed MF, Abulkhair HS, Elkady H, El-Adl K. Design, synthesis, in silico ADMET profile and GABA-A docking of novel phthalazines as potent anticonvulsants. Arch Pharm (Weinheim). 2019;352(5). Available from: https://pubmed.ncbi.nlm.nih.gov/30989729/
  34. Ayyad RR, Nejm AM, Hassan YAA, Ayyad AR. Mechanism of Action of Many Drugs Depend on Enzyme Inhibition. Curr Res Med Sci. 2023;2(4):1-9. Available from: https://www.pioneerpublisher.com/crms/article/view/494
  35. El-Adl K, El-Helby AGA, Sakr H, Ayyad RR, Mahdy HA, Nasser M, et al. Design, synthesis, molecular docking, anticancer evaluations, and in silico pharmacokinetic studies of novel 5-[(4-chloro/2,4-dichloro) benzylidene] thiazolidine-2,4-dione. Arch Pharm. 2021;354(2):2000279. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/ardp.202000279
  36. El-Helby AGA, Sakr H, Ayyad RRA, El-Adl K, Ali MM, Khedr F. Design, synthesis, in vitro anti-cancer activity, ADMET profile and molecular docking of novel triazolo [3,4-a] phthalazine derivatives targeting VEGFR-2 enzyme. Anti-Cancer Agents Med Chem. 2018;18(8):1184-1196. Available from: https://www.ingentaconnect.com/content/ben/acamc/2018/00000018/00000008/art00015
  37. Sakr H, Otify I, Ayyad RR, Elwan A. VEGFER-2 INHIBITORS AND QUINAZOLINE-BASED ANTICANCER AGENTS. Al-Azhar J Pharm Sci. 2022;68(2):111-129. Available from: https://ajps.journals.ekb.eg/article_332170.html
  38. Abdel-Aziz AA, Abou-Zeid LA, ElTahir KEH, Ayyad RR, El-Sayed MA, El-Azab AS. Synthesis, anti-inflammatory, analgesic, COX-1/2 inhibitory activities and molecular docking studies of substituted 2-mercapto-4(3H)-quinazolinones. Eur J Med Chem. 2016;121:410-421. Available from: https://pubmed.ncbi.nlm.nih.gov/27318118/
  39. El-Helby AGA, Ayyad RR, El-Adl K, Elwan A. Quinoxalin-2(1H)-one derived AMPA-receptor antagonists: Design, synthesis, molecular docking and anticonvulsant activity. Med Chem Res. 2017;26:2967-2984. Available from: https://link.springer.com/article/10.1007/s00044-017-1996-5
  40. Elhelby AA, Ayyad RR, Zayed MF. Synthesis and biological evaluation of some novel quinoxaline derivatives as anticonvulsant agents. Arzneimittelforschung. 2011;61(7):379-81. Available from: https://pubmed.ncbi.nlm.nih.gov/21899204/
  41. Eldehna WM, Abou-Seri SM, El Kerdawy AM, Ayyad RR, Hamdy AM, Ghabbour HA, et al. Increasing the binding affinity of VEGFR-2 inhibitors by extending their hydrophobic interaction with the active site: Design, synthesis and biological evaluation of 1-substituted-4-(4-methoxybenzyl)phthalazine derivatives. Eur J Med Chem. 2016 May 4;113:50-62. doi: 10.1016/j.ejmech.2016.02.029. PMID: 26922228. Available from: https://pubmed.ncbi.nlm.nih.gov/26922228/
  42. El-Helby AA, Ayyad RRA, El-Adl K, Elkady H. Phthalazine-1,4-dione derivatives as non-competitive AMPA receptor antagonists: design, synthesis, anticonvulsant evaluation, ADMET profile and molecular docking. Mol Divers. 2019 May;23(2):283-298. doi: 10.1007/s11030-018-9871-y. PMID: 30168051. Available from: https://pubmed.ncbi.nlm.nih.gov/30168051/
  43. El-Helby AA, Ayyad RRA, Sakr H, El-Adl K, Ali MM, Khedr F. Design, Synthesis, Molecular Docking, and Anticancer Activity of Phthalazine Derivatives as VEGFR-2 Inhibitors. Arch Pharm (Weinheim). 2017 Dec;350(12). doi: 10.1002/ardp.201700240. PMID: 29131379. Available from: https://pubmed.ncbi.nlm.nih.gov/29131379/
  44. El-Helby AA, Sakr H, Ayyad RR, Mahdy HA, Khalifa MM, Belal A, et al. Design, synthesis, molecular modeling, in vivo studies and anticancer activity evaluation of new phthalazine derivatives as potential DNA intercalators and topoisomerase II inhibitors. Bioorg Chem. 2020;103:104233. Available from: https://pubmed.ncbi.nlm.nih.gov/32882440/
  45. El-Helby AA, Ibrahim MK, Abdel-Rahman AA, Ayyad RRA, Menshawy MA, et al. Synthesis, molecular modeling, and anticonvulsant activity of benzoxazole derivatives. Al-Azhar J Pharm Sci. 2017;40:252-270.
  46. El-Helby AGA, Ayyad RRA, El-Adl K, Sakr H, Abd-Elrahman AA, Eissa IH, et al. Design, molecular docking, and synthesis of some novel 4-acetyl-1-substituted-3,4-dihydroquinoxalin-2(1H)-one derivatives for anticonvulsant evaluation as AMPA antagonists. Med Chem Res. 2016;25:3030-3046. Available from: https://www.infona.pl/resource/bwmeta1.element.springer-doi-10_1007-S00044-016-1723-7
  47. Ayyad RRA, Sakr H, El-Gamal K. Synthesis, modeling and anticonvulsant activity of some phthalazinone derivatives. Am J Org Chem. 2016;6(1):29-38. Available from: http://article.sapub.org/10.5923.j.ajoc.20160601.04.html
  48. Ayyad RR, Sakr HM, El-Gamal KM, Eissa IH, et al. Anti-Inflammatory, Proton Pump Inhibitor and Synthesis of Some New Benzimidazole Derivatives. Der Chemica Sinica. 2017;8(1):184-197. Available from: https://www.imedpub.com/articles/antiinflammatory-proton-pump-inhibitor-and-synthesis-of-some-newbenzimidazole-derivatives.pdf
  49. Abdel-Aziz AA, El-Azab AS, Abou-Zeid LA, ElTahir KE, Abdel-Aziz NI, Ayyad RR, Al-Obaid AM. Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies. Eur J Med Chem. 2016;115:121-131. Available from: https://pubmed.ncbi.nlm.nih.gov/26999325/
  50. Eldehna WM, Salem R, Elsayed ZM, Al-Warhi T, Knany HR, Ayyad RR, et al. Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer. J Enzyme Inhib Med Chem. 2021;36(1):1424-1435. Available from: https://pubmed.ncbi.nlm.nih.gov/34176414/
  51. Zayed MF, Ayyad RR. Some novel anticonvulsant agents derived from phthalazinedione. Arzneimittelforschung. 2012;62(11):532-536. Available from: https://pubmed.ncbi.nlm.nih.gov/22956351/
  52. Eldehna WM, Abo-Ashour MF, Al-Warhi T, Al-Rashood ST, Alharbi A, Ayyad RR, et al. Development of 2-oindolin-3-ylidene-indole-3-carbohydrazide derivatives as novel apoptotic and anti-proliferative agents towards colorectal cancer cells. J Enzyme Inhib Med Chem. 2021;36(1):319-328. Available from: https://pubmed.ncbi.nlm.nih.gov/33345633/

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