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.
Acknowledgement
This work was performed in partial fulfillment of the requirements for Pharm. D. of N. Alimoradi, in Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
Disclosure statement
The authors declare that they have no conflict of interests.
Funding
The financial support [Grant No. 92047] from the Research Council of Kermanshah University of Medical Sciences is gratefully acknowledged.