2. Academic Validation
  3. Bisthioureas of pimelic acid and 4-methylsalicylic acid derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP): Synthesis and molecular docking studies

Bisthioureas of pimelic acid and 4-methylsalicylic acid derivatives as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP) and intestinal alkaline phosphatase (IAP): Synthesis and molecular docking studies

  • Bioorg Chem. 2020 Aug;101:103996. doi: 10.1016/j.bioorg.2020.103996.
Amara Mumtaz 1,  Kiran Saeed 2,  Abid Mahmood 3,  Sumera Zaib 3,  Aamer Saeed 4,  Julie Pelletier 5,  Jean Sévigny 6,  Jamshed Iqbal 7
Affiliations

Affiliations

  • 1 Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: amaramumtaz@cuiatd.edu.pk.
  • 2 Department of Chemistry, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
  • 3 Center for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
  • 4 Department of Chemistry, Quaid-i-Azam University Islamabad, Pakistan.
  • 5 Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada.
  • 6 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.
  • 7 Center for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: drjamshed@cuiatd.edu.pk.
PMID: 32563965 DOI: 10.1016/j.bioorg.2020.103996
Abstract

Alkaline phosphatases (ALPs) are membrane bound metalloenzymes, distributed all over the body. Recent studies have revealed that by targeting ALPs can lead towards the treatment of many deadliest diseases including cardiac, cancerous and brain diseases. Thioureas and their derivatives are of considerable significance and are privileged scaffolds in medicinal chemistry. They show a wide range of pharmacological activities such as Antibacterial, antiparasitic, anti-inflammatory and antioxidants etc. On the other hand, salicylic acid and its derivatives are known for its broad spectrum of activities. The work presented comprises of synthesis of N-acyl-N'-aryl substituted bisthioureas of pimelic acid (1-7) and 3,5-dimethyl pyrazole (11), 1-aroyl-3-aryl thiourea (12) and 1,3,4-oxadiazole (13) derivatives of 4-methyl salicylic acid. Structures of all the synthesized compounds were characterized by FT-IR and 1H NMR spectroscopic analysis. Synthesized compounds were evaluated for their alkaline phosphatases inhibition potential and exhibited high potency as well as selectivity towards h-TNAP and h-IAP. Compound 7 and 12 which were the bisthiourea derivative of pimmelic acid and thiourea derivative of 4-methyl salicylic acid, respectively, showed excellent selectivity against h-TNAP and h-IAP, respectively.

Keywords

Alkaline phosphatase inhibitors; Pimelic acid; Salicylic acid; Thiourea.

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