Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties—Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities

Abstract

In the search for new bioactive compounds, a methodology based on combining two molecules with biological properties into a new hybrid molecule was used to design and synthesize of a series of ten indole derivatives bearing imidazole, benzothiazole-2-thione, or benzoxazole-2-thione moieties at the C-3 position. The compounds were spectroscopically characterized and tested for their antioxidant, antibacterial, and fungicidal activities. The crystal structures were determined for five of them. Comparison of the closely related structures containing either benzothiazole-2-thione or benzoxazole-2-thione clearly shows that the replacement of -S- and -O- ring atoms modify molecular conformation in the crystal, changes intermolecular interactions, and has a severe impact on biological activity. The results indicate that indole-imidazole derivatives with alkyl substituent exhibit an excellent cytoprotective effect against AAPH-induced oxidative hemolysis and act as effective ferrous ion chelating agents. The indole-imidazole compound with chlorine atoms inhibited the growth of fungal strains: Coriolus versicolor (Cv), Poria placenta (Pp), Coniophora puteana (Cp), and Gloeophyllum trabeum (Gt). The indole-imidazole derivatives showed the highest antibacterial activity, for which the largest growth-inhibition zones were noted in M. luteus and P. fluorescens cultures. The obtained results may be helpful in the development of selective indole derivatives as effective antioxidants and/or antimicrobial agents.

Synthesis, Structure and Biological Activity of Indole–Imidazole Complexes with ZnCl2: Can Coordination Enhance the Functionality of Bioactive Ligands?

“…The indole–imidazole ligands, including (InIm) ( L1 ), (InMeIm) ( L2 ), (IniPrIm) ( L3 ), (InEtMeIm) ( L4 ), (InPhIm) ( L5 ) and (InBzIm) ( L6 ), where InIm is 3-((1H-imidazol-1-yl)methyl)-1H-indole (see Scheme 1 ), were synthesized from gramine and substituted imidazoles according to our previous report [ 16 ]. The reactions of the obtained ligands with anhydrous ZnCl 2 afforded complexes 1 – 6 in good yields ( Scheme 1 ).…”

“…Recently, indole–imidazole hybrids have attracted more attention. This type of conjugate shows antioxidant, antimicrobial, and anticancer properties [ 15 , 16 , 17 , 18 , 19 , 20 ]. As drugs, they have been used as α-glucosidase inhibitors [ 21 ] and selective 5-HT7R agonists [ 22 ].…”

“…Although zinc does not directly interact with the oxidant, it may indirectly reduce its effect by protecting cells from the oxidative damage and stabilizing the molecular structure of the cell membrane [ 44 ]. Our previous work has shown that indole derivatives with a substituent at the C-3 position protect human erythrocytes against oxidative hemolysis in vitro [ 8 , 16 , 45 , 46 ]. In addition, indole–imidazole compounds exhibit excellent iron complexing properties [ 16 ].…”

“…Our previous work has shown that indole derivatives with a substituent at the C-3 position protect human erythrocytes against oxidative hemolysis in vitro [ 8 , 16 , 45 , 46 ]. In addition, indole–imidazole compounds exhibit excellent iron complexing properties [ 16 ].…”

“…The cytoprotective activity of the derivatives was evaluated in vitro by determining the inhibition of oxidative-hemolysis, which is induced by free radicals generated by 2,2′-azobis(2-amidinopropane hydrochloride) (AAPH). Human erythrocytes (red blood cells, RBCs), due to the lack of any intracellular membrane systems, are widely used as model cells to assess the protective activity of the cell membrane-incorporating compounds under oxidative stress conditions [ 8 , 16 , 45 , 46 ]. In addition, the complexes were screened for antibacterial and antifungal properties.…”