A series of novel (3-sulfonamido) phenyloxindoles were prepared from (3H-indene-1,2-dione) isatin via reductive amination, reduction followed by reaction of resulting amine with different arenesulfonyl chloride and screened for their Proinflammatory cytokines inhibition (TNF-α and IL-6) on lipopolysaccharide stimulated peripheral blood mononuclear cells. The sulfonamide derivative such as compound 5d, 5h and 5i exhibited promising inhibition of the release of two cytokines TNF-α and IL-6 with IC-50 values raging over 1.9-2.6 and 1.2-1.7 respectively and thus proved to be potent TNF-α and IL-6 inhibitor.