No abstract

Where a licence is displayed above, please note the terms and conditions of the licence govern your use of this document. When citing, please reference the published version. Take down policy While the University of Birmingham exercises care and attention in making items available there are rare occasions when an item has been uploaded in error or has been deemed to be commercially or otherwise sensitive.

Several novel 1,1-disubstituted-8-hydroxynaphthalen-2(1H)-ones have been efficiently synthesized via a two-step sequence from 2-hydroxy-1-naphthaldehyde oxime. The methodology involves oxidative ring closure and alkoxylation to 3a-alkoxynaphtho[1,8-de][1,2]oxazin-4(3aH)-ones, followed by thermal ring-opening. Both thermal and microwave irradiation conditions were used. A novel one-pot reaction of oxime to 8-isopropoxynaphthalene-1,7-diol using microwave irradiation is also reported.

No abstract

The selectivity of certain benzophenones and their carbonyl N-analogues was investigated towards the human GSTP1-1 allozymes A, B and C involved in MDR. The allozymes were purified from extracts derived from E. coli harbouring the plasmids pEXP5-CT/TOPO-TA-hGSTP1*A, pOXO4-hGSTP1*B or pOXO4-hGSTP1*C. Compound screening with each allozyme activity indicated three compounds with appreciable inhibitory potencies, 12 and 13 with P1-1A 62% and 67%, 11 and 12 with P1-1C 51% and 70%, whereas that of 15 fell behind with P1-1B (41%). These findings were confirmed by IC50 values (74-125 μm). Enzyme inhibition kinetics, aided by molecular modelling and docking, revealed that there is competition with the substrate CDNB for the same binding site on the allozyme (Ki(13/A)  = 63.6 ± 3.0 μm, Ki(15/B)  = 198.6 ± 14.3 μm, and Ki(11/C)  = 16.5 ± 2.7 μm). These data were brought into context by an in silico structural comparative analysis of the targeted proteins. Although the screened compounds showed moderate inhibitory potency against hGSTP1-1, remarkably, some of them demonstrated absolute isoenzyme and/or allozyme selectivity.