title: Diethylalkylsulfonamido(4-methoxyphenyl)methyl)phosphonate/phosphonic acid derivatives act as acid phosphatase inhibitors: synthesis accompanied by experimental and molecular modeling assessments.
abstract: Purple acid phosphatases (PAPs) are binuclear metallo-hydrolases that have been isolated from various mammals, plants, fungi and bacteria. In mammals, PAP activity is associated with bone resorption and can lead to bone metabolic disorders such as osteoporosis; thus human PAP is an attractive target to develop anti-osteoporotic drugs. The aim of the present study was to investigate inhibitory effect of synthesized diethylalkylsulfonamido(4-methoxyphenyl)methyl)phosphonate/phosphonic acid derivatives as potential red kidney bean PAP (rkbPAP) inhibitors accompanied by experimental and molecular modeling assessments. Enzyme kinetic data showed that they are good rkbPAP inhibitors whose potencies improve with increasing alkyl chain length. Hexadecyl derivatives, as most potent compounds (Ki= 1.1 µM), inhibit rkbPAP in the mixed manner, while dodecyl derivatives act as efficient noncompetitive inhibitor. Also, analysis by molecular modeling of the structure of the rkbPAP-inhibitor complexes reveals factors, which may be important for the determination of inhibition specificity.
authors: a Student Research Committee , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Nahid
authors: N
authors: Alimoradi
authors: b Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Mohammad Reza
authors: MR
authors: Ashrafi-Kooshk
authors: c Nano Drug Delivery Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Mohsen
authors: M
authors: Shahlaei
authors: b Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Shabnam
authors: S
authors: Maghsoudi
authors: d Pharmaceutical Sciences Research Center, Faculty of Pharmacy , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Hadi
authors: H
authors: Adibi
authors: e The University of Queensland, School of Chemistry and Molecular Biosciences , St. Lucia , QLD , Australia.
authors: Ross P
authors: RP
authors: McGeary
authors: b Medical Biology Research Center , Kermanshah University of Medical Sciences , Kermanshah , Iran.
authors: Reza
authors: R
authors: Khodarahmi
mesh_terms: D000135:Acid Phosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D027805:Phaseolus / Q000201:enzymology; D010757:Phosphorous Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D006023:Glycoproteins; D010757:Phosphorous Acids; C091137:purple acid phosphatase; D000135:Acid Phosphatase
keywords: Acid phosphatase; enzyme inhibition; phosphonic acid; synthesis