Synthesis, Characterization and Biological Studies of Novel Guanidines and Their Complexes

Abstract

Two series of substituted guanidines (a 1 -a 32 & b 1 -b 32 ) and their copper(II) complexes of general formula [κ 2 (O, N)-C 6 H 5 CONHC(NHR 1 )NR 2 ] 2 Cu(II) where, R 1 = phenyl (A 1 - A 32 ), 2-chlorophenyl (B 1 -B 32 ) and R 2 = alkyl/aryl groups, have been synthesized and characterized by using elemental analysis, FT-IR, multinuclear ( 1 H and 13 C) NMR spectroscopy and magnetic susceptibility measurements. Single crystal XRD was used for structural elucidation of some of the synthesized guanidine ligands and their copper(II) complexes. Based on the single crystal X-ray analysis most of the synthesized guanidine ligands were stabilized by intermolecular as well as intramolecular hydrogen bonding. All the complexes are mononuclear in solid state and copper adopts a regular square planar geometry with slight distortion in few cases, while N,N',N"-trisubstituted guanidine ligands chelate the Cu(II) atom through oxygen and nitrogen with ligand to metal ratio 2:1. DFT studies have been used to assess the location of the protons in free ligands, however calculations have shown that in all cases, hydrogen bonding from either of the N-H groups gives conformations that are very similar in energy. The synthesized guanidines and their complexes were also screened for urease inhibition, antileishmanial, anticancer and antifungal activities. The complexes exhibited a better usease inhibition activity than the respective guanidines and compound A 7 was found to be the most active with IC 50 = 4.8 ± 0.05 μM (IC 50 for standard thiourea is 21.0 ± 0.1 μM). These compounds were also screened for their brine shrimp lethality assay, a 1 and A 28 were found to be more toxic with the ID 50 value 1.701 ppm. In potato disc antitumour assay guanidines and complexes have shown the excellent activity comparable with the vincristine, used as standard drug while, in vitro cytotoxicity against human cell lines carcinomas A498, EVSAT, H226, IGROV, M19, MCF-7 and WIDR these compounds show moderate cytotoxicity against these cell lines as compared to the standard chemotherapeutic drugs. These compounds were also tested for antifungal and antileishmanial activities and show moderate to good antifungal activity but no significant antileishmanial activity.