Novel Bromo and methoxy substituted Schiff base complexes of Mn(II), Fe(III), and Cr(III) for anticancer, antimicrobial, docking, and ADMET studies

In this study, four new Mn (II), Fe (III), and Cr (III) complexes with two Schiff base ligands namely, 4-bromo-2- (E) -[4- (2-hydroxyethyl) phenyliminomethyl]phenol (HL1) and 2- (E) -[4- (2-hydroxyethyl) phenyliminomethyl]-4-methoxy phenol (HL2) have been synthesized and characterized. Different analytical and spectral methods have been used to characterize the ligands and their complexes. General formulas of M (L) Cl2 (H2O) 2 for FeL1, CrL1 and CrL2, and M (L) Cl (H2O) 3 for MnL2 were proposed. HOMO and LUMO energies, as well as the electrical characteristics, have been calculated using DFT/B3LYP calculations with Gaussian 09 program. The optimized lowest energy configurations of the complexes are proven. The disc diffusion technique was used to test the pharmacological activities' antibacterial efficacy against diverse bacterial and fungus species. The MTT technique was used to assess the in vitro cytotoxicity of the ligands and their metal complexes on the Hep-G2 human liver carcinoma cell line and the MCF-7 human breast cancer cell line. All compounds displayed better activity compared to the free ligands. MnL2 complex showed predominant activity when compared to the other complexes with an IC50 value of 2. 6 ± 0. 11 μg/ml against Hep-G2, and against MCF-7 the IC50 value was 3. 0 ± 0. 2 μg/ml which is less than the standard drug cisplatin (4. 0 μg/ml). UV-vis electronic spectrum and gel electrophoresis techniques have been used to investigate the compounds' affinity to bind and cleavage CT-DNA. The interaction's binding constants, or Kb, have been identified, and it was discovered that the new complexes' binding affinities are in the order of FeL1 > MnL2 > CrL2 > CrL1, and the binding mechanism has been suggested. To assess the kind of binding and binding affinity of the investigated drugs with human DNA, a molecular docking study was carried out (PDB: 1bna). The acquired results supported the intercalation binding mechanism proposed in the experimental part and revealed that complexes may be inserted into the DNA molecule to stop DNA replication. According to ADMET data, the synthesized compounds have a high bioavailability profile and their physicochemical and pharmacological features remained within Lipinski's RO5 predicted limitations.