New Schiff bases (E)-N-(3,4-dimethylisoxazol-5-yl)-4-(2-hydroxy-3-methoxybenzylidene) amino) benzenesulfonamide (LI), (E)-N-(3,4-d imethylisoxazol-5-yl)-4-(2-hydroxy-4-methoxybenzylidene) amino)benzenesulfonamide (L2) and (E)-4-((4-methoxy-2-hydroxybenzylidene)amino)-N-(5-methylisoxazol-3-yl)benzene sulfonamide (L3) derived from sulfamethoxazole (S1)/sulfisoxazole (S2) and substituted salicylaldehydes and their Pd (II), Cu (II) complexes were synthesized for the first time. The synthesized compounds were characterized by FT-IR, H-1-C-13 NMR, LC-MS, magnetic susceptibility, conductivity measurements and thermal analysis (TGA). The complexes having general composition of [ML2] were found. The results of elemental analysis showed 1:2 (metal/ligand) stochiometry for all the complexes. Magnetic and spectral data indicate a square planar geometry for Pd (II) complexes and a distorted tetrahedral geometry for Cu (II) complexes. H-1 and C-13 shielding tensors for crystal structure were calculated with GIAO/DFT/B3LYP/6-311++G(d,p) methods in CDCl3. The nonlinear optical (NLO) properties and frontier molecular orbitals have been investigated by B3LYP/6-311++G(d,p) and B3LYP/LanL2DZ level of theory. The ligands and their metal chelates have been screened for their antimicrobial activities using the microdilution method (as MICs) method against the selected Staphylococcus aureus, Eschericha coli, Klebsiella pneumonia and Stenotrophomonas Maltophilia. The inhibition activities of these compounds on carbonic anhydrase II (CA II) and carbonic anhydrase I (CAI) have been investigated by comparing IC50 values, and it has been observed that Cu (II) complex (IC50 values = 6-22 mu M range) and Pd(II) (IC50 values = 16-138 mu M range) have had very high inhibition potencies on enzymes than ligands (not inhibition for CAI, IC50 values =173-346 mu M range). (C) 2018 Elsevier B.V. All rights reserved.