TY - JOUR
T1 - Identification of novel chromone based sulfonamides as highly potent and selective inhibitors of alkaline phosphatases
AU - Al-Rashida, Mariya
AU - Raza, Rabia
AU - Abbas, Ghulam
AU - Shah, Muhammad Shakil
AU - Kostakis, George E.
AU - Lecka, Joanna
AU - Sev́igny, Jean
AU - Muddassar, Muhammad
AU - Papatriantafyllopoulou, Constantina
AU - Iqbal, Jamshed
PY - 2013
Y1 - 2013
N2 - A new series of structurally diverse chromone containing sulfonamides has been developed. Crystal structures of three representative compounds (2a, 3a and 4a) in the series are reported. All compounds were screened for their inhibitory potential against alkaline phosphatases (ALPs). Two main classes of ALP isozymes were selected for this study, the tissue non-specific alkaline phosphatase (TNALP) from bovine and porcine source and the tissue-specific intestinal alkaline phosphatases (IALPs) from bovine source. All sulfonamide compounds had a marked preference for IALP (Ki, up to 0.01 ± 0.001 μM) over TNALPs. Kinetics studies of the compounds showed competitive mode of inhibition. Molecular docking studies were carried out in order to characterize the selective inhibition of the compounds. An additional interesting aspect of these chromone sulfonamides is their inhibitory activity against ecto-5′-nucleotidase enzyme.
AB - A new series of structurally diverse chromone containing sulfonamides has been developed. Crystal structures of three representative compounds (2a, 3a and 4a) in the series are reported. All compounds were screened for their inhibitory potential against alkaline phosphatases (ALPs). Two main classes of ALP isozymes were selected for this study, the tissue non-specific alkaline phosphatase (TNALP) from bovine and porcine source and the tissue-specific intestinal alkaline phosphatases (IALPs) from bovine source. All sulfonamide compounds had a marked preference for IALP (Ki, up to 0.01 ± 0.001 μM) over TNALPs. Kinetics studies of the compounds showed competitive mode of inhibition. Molecular docking studies were carried out in order to characterize the selective inhibition of the compounds. An additional interesting aspect of these chromone sulfonamides is their inhibitory activity against ecto-5′-nucleotidase enzyme.
KW - Alkaline phosphatase inhibitors
KW - Chromones
KW - Ecto-5′-nucleotidase inhibitors
KW - Molecular docking
KW - Structure activity relationships (SARs)
KW - Sulfonamides
UR - https://www.scopus.com/pages/publications/84879817514
U2 - 10.1016/j.ejmech.2013.06.015
DO - 10.1016/j.ejmech.2013.06.015
M3 - Article
SN - 0223-5234
VL - 66
SP - 438
EP - 449
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
ER -