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Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities.
Bioorg Chem. 2020 07; 100:103827.BC

Abstract

Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents.

Authors+Show Affiliations

Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore, Pakistan.Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore, Pakistan; Department of Chemistry, University of Sahiwal, Sahiwal 57000, Pakistan.Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan.Department of Chemistry and Chemical Engineering, Syed Babar Ali School of Science and Engineering, Lahore University of Management Sciences, Lahore, Pakistan.Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia.Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Nerus, Terengganu, Malaysia.Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada.Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada; Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada.Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: drjamshed@cuiatd.edu.pk.Department of Chemistry, Forman Christian College (A Chartered University), Ferozepur Road, Lahore, Pakistan. Electronic address: mariyarashida@fccollege.edu.pk.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32402802

Citation

Younus, Hafiza Amna, et al. "Sulfonylhydrazones: Design, Synthesis and Investigation of Ectonucleotidase (ALP & e5'NT) Inhibition Activities." Bioorganic Chemistry, vol. 100, 2020, p. 103827.
Younus HA, Hameed A, Mahmood A, et al. Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities. Bioorg Chem. 2020;100:103827.
Younus, H. A., Hameed, A., Mahmood, A., Khan, M. S., Saeed, M., Batool, F., Asari, A., Mohamad, H., Pelletier, J., Sévigny, J., Iqbal, J., & Al-Rashida, M. (2020). Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities. Bioorganic Chemistry, 100, 103827. https://doi.org/10.1016/j.bioorg.2020.103827
Younus HA, et al. Sulfonylhydrazones: Design, Synthesis and Investigation of Ectonucleotidase (ALP & e5'NT) Inhibition Activities. Bioorg Chem. 2020;100:103827. PubMed PMID: 32402802.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sulfonylhydrazones: Design, synthesis and investigation of ectonucleotidase (ALP & e5'NT) inhibition activities. AU - Younus,Hafiza Amna, AU - Hameed,Abdul, AU - Mahmood,Abid, AU - Khan,Muhammad Siraj, AU - Saeed,Muhammad, AU - Batool,Farwa, AU - Asari,Asnuzilawati, AU - Mohamad,Habsah, AU - Pelletier,Julie, AU - Sévigny,Jean, AU - Iqbal,Jamshed, AU - Al-Rashida,Mariya, Y1 - 2020/04/08/ PY - 2019/11/16/received PY - 2020/03/16/revised PY - 2020/04/05/accepted PY - 2020/5/14/pubmed PY - 2021/3/9/medline PY - 2020/5/14/entrez KW - Alkaline phosphatase KW - Chromen-2-one KW - Ecto-5ʹ-nucleotidase KW - Ectonucleotidase inhibitors KW - Sulfonylhydrazone SP - 103827 EP - 103827 JF - Bioorganic chemistry JO - Bioorg Chem VL - 100 N2 - Medicinal importance of the sulfonylhydrazones is well-evident owing to their binding ability with zinc containing metalloenzymes. In the present study, we have synthesized different series of sulfonylhydrazones by using facile synthetic methods in good to excellent yield. All the successfully prepared sulfonylhydrazones were screened for ectonucleotidase (ALP & e5'NT) inhibitory activity. Among the chromen-2-one scaffold based sulfonylhydrazones, the compounds 7 was found to be most potent inhibitor for h-TNAP (human tissue non-specific alkaline phosphatase) and h-IAP (human intestinal alkaline phosphatase) with IC50 values of 1.02 ± 0.13 and 0.32 ± 0.0 3 µM respectively, compared with levamisole (IC50 = 25.2 ± 1.90 µM for h-TNAP) and l-phenylalanine (IC50 = 100 ± 3.00 µM for h-IAP) as standards. Further, the chromen-2-one based molecule 5a showed excellent activity against h-ecto 5'-NT (human ecto-5'-nucleotidase) with IC50 value of 0.29 ± 0.004 µM compared to standard, sulfamic acid (IC50 = 42.1 ± 7.8 µM). However, among the series of phenyl ring based sulfonylhydrazones, compound 9d was found to be most potent against h-TNAP and h-IAP with IC50 values of 0.85 ± 0.08 and 0.52 ± 0.03 µM, respectively. Moreover, in silico studies were also carried to demonstrate their putative binding with the target enzymes. The potent compounds 5a, 7, and 9d against different ectonucleotidases (h-ecto 5'-NT, h-TNAP, h-IAP) could potentially serve as lead for the development of new therapeutic agents. SN - 1090-2120 UR - https://www.unboundmedicine.com/medline/citation/32402802/Sulfonylhydrazones:_Design_synthesis_and_investigation_of_ectonucleotidase__ALP_&_e5'NT__inhibition_activities_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0045-2068(19)31957-1 DB - PRIME DP - Unbound Medicine ER -