2. Academic Validation
  3. Synthesis, biological evaluation, and docking studies of new pyrazole-based thiourea and sulfonamide derivatives as inhibitors of nucleotide pyrophosphatase/phosphodiesterase

Synthesis, biological evaluation, and docking studies of new pyrazole-based thiourea and sulfonamide derivatives as inhibitors of nucleotide pyrophosphatase/phosphodiesterase

  • Bioorg Chem. 2020 Jun;99:103783. doi: 10.1016/j.bioorg.2020.103783.
Saif Ullah 1,  Mohammed I El-Gamal 2,  Sumera Zaib 1,  Hanan S Anbar 3,  Seyed-Omar Zaraei 4,  Rawan M Sbenati 4,  Julie Pelletier 5,  Jean Sévigny 6,  Chang-Hyun Oh 7,  Jamshed Iqbal 8
Affiliations

Affiliations

  • 1 Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan.
  • 2 Department of Medicinal Chemistry, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Medicinal Chemistry, Faculty of Pharmacy, University of Mansoura, Mansoura 35516, Egypt.
  • 3 Department of Clinical Pharmacy and Pharmacotherapeutics, Dubai Pharmacy College for Girls, Dubai 19099, United Arab Emirates.
  • 4 Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates.
  • 5 Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada.
  • 6 Département de microbiologie-infectiologie et d'immunologie, Faculté de Médecine, Université Laval, Québec, QC G1V 0A6, Canada; Centre de Recherche du CHU de Québec - Université Laval, Québec, QC G1V 4G2, Canada.
  • 7 Center for Biomaterials, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul 130-650, Republic of Korea; Department of Biomolecular Science, Korea University of Science and Technology, 113 Gwahangno, Yuseong-gu, Daejeon 305-333, Republic of Korea. Electronic address: choh@kist.re.kr.
  • 8 Centre for Advanced Drug Research, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan. Electronic address: drjamshed@cuiatd.edu.pk.
PMID: 32224334 DOI: 10.1016/j.bioorg.2020.103783
Abstract

A series of six compounds (1a-f) possessing pyridine-pyrazole-benzenethiourea or pyridine-pyrazole-benzenesulfonamide scaffold were synthesized. The target compounds were screened to evaluate their inhibitory effect on human nucleotide pyrophosphatase/phosphodiesterase 1 and -3 (ENPP1 and ENPP3) isoenzymes. Compounds 1c-e were the most potent inhibitors of ENPP1 with sub-micromolar IC50 values (0.69, 0.18, and 0.40 µM, respectively. Moreover, compound 1b was the most potent inhibitor of ENPP3 (IC50 = 0.21 µM). They were much more potent than the reference standard inhibitor, suramin (IC50 values against ENPP1 and -3 were 7.77 and 0.89 µM, respectively). Furthermore, all the six compounds were investigated for cytotoxic effect against cancerous cell lines (HeLa, MCF-7, and 1321N1) and normal cell line (BHK-21). Compound 1e was active against all the three Cancer cell lines, however, showed preferential cytotoxicity against MCF-7 (IC50 = 16.05 µM), which is comparable to the potency of cisplatin. All the tested compounds exhibited low or negligible cytotoxic effect against the normal cells. They have the merit of superior selectivity towards Cancer cells than normal cells compared to cisplatin. The relative selectivity and potency of the inhibitors was justified by molecular docking studies. All the docked structures showed considerable binding interactions with Amino acids residues of active sites of ENPP isoenzymes.

Keywords

Cytotoxic studies; Molecular docking and simulations; Nucleotide pyrophosphatase/phosphodiesterase; Pyridine-pyrazole-benzenesulfonamide; Pyridine-pyrazole-benzenethiourea.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z