A series of novel 3-aroyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazines 15-28 as potential HIV-1 integrase (IN) inhibitors have been synthesized by the reduction of 3-aroyl-1,1-dioxo-1,4,2-benzodithiazines 1-14 with benzenesulfonyl hydrazide. All the compounds 15-28 inhibited IN mediated strand transfer reaction with IC(50) values ranging from 3 to 30 microM. The 3-(4-bromobenzoyl)-6-chloro-7-methyl-2,3-dihydro-1,1-dioxo-1,4,2-benzodithiazine 17 with the IC(50) values of 4+/-1 and 3+/-1 microM for 3'-processing and strand transfer, respectively, was the most potent. Compound 17 as well its analogues were 5-20-fold less potent in Y99S and H114A mutants, implicating these residues as potential drug-binding site. This is a first report implicating Y99S and H114A of IN core domain in drug-binding interactions.