title: Quantitative structure-activity relationship study of 5-iodo- and diaryl-analogues of tubercidin: inhibitors of adenosine kinase.
abstract: The adenosine kinase inhibitory (AKI) activity of 5-iodo and diaryl analogues of tubercidin is quantitatively analyzed using Fujita-Ban and Hansch type analyses. The Fujita-Ban analysis being a non-parametric approach assigned the highest contribution to Cl at the X-position, C6H4-4-Cl, C6H5, 2-furanyl and I at the Y-position and CH2NH2 and CH3 at the Z-position. In addition, a OH substituent at the C-position also emerged as a better choice possibly due to its engagement in hydrogen bonding with some active site function. Thus a compound having Cl, C6H4-4-Cl, CH2NH2 and OH respectively at X-, Y-, Z- and C-positions is predicted to have a potency nearly 1.5 orders of magnitude higher than the most potent compound of the parent data set. The Hansch type analysis, on the other hand, is a parametric approach and is carried out on two sub-sets of original compounds. This sub-division is based on size and nature of the substituents present at the X- and Y-positions. For the compounds in the first sub-set the derived significant correlation equation suggested that the substituent at the Y-position exhibiting a higher field effect and a substituent such as Cl and CH2NH2 at X- and Z-positions, respectively, are important for a compound to show increased AKI activity. Thio/alkylthio at X and CH2OCH3 at Z, on the other hand, lead to a detrimental effect. Similarly for the compounds in the second subset, the derived significant correlation equation showed that a substituent at the X-position having a higher negative field effect, a substituent at the Y-position having bulky groups and the C-position occupied by a OH group are essential for enhancement of the activity of a compound.
authors.affiliation: Department of Chemistry, S.K. Government College, Sikar 332 001, India. singhp1_skc_india@rediffmail.com
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.forename: B K
authors.initials: BK
authors.lastname: Sharma
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015195:Drug Design; D007455:Iodine / Q000737:chemistry*; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D007455:Iodine; D000248:Adenosine Kinase; D014372:Tubercidin