Benzimidazole – Schiff bases and their complexes: synthesis, anticancer activity and molecular modeling as Aurora kinase inhibitor

Abstract

A new series of Schiff bases containing benzіmidazole moiety 11-17 were synthesized by the reaction of 4-(1H-benzо[d]іmіdazоl-2-yl)anіline (1) with different aromatic aldehydes (4-10) via conventional heating and microwave irradiation methods. The structures of the novel Schiff bases were characterized by using different spectral data. Also, metal complexes 18-21 of compound 13 were synthesized, and their structure was confirmed by spectral measurements (IR, NMR, UV), molar conductivity, magnetic susceptibility and thermo-gravimetric analysis. The novel synthesized ligand 13 and its complexes 18-21 were tested for their in vitro antitumor activities towards breast, liver and lung cancer cell lines. Also, the acute toxicity of the prepared compounds 13 and 18-21 was determined in vivo. The results showed that the newly synthesized compounds 13 and 18-21 exhibited a significant activity against cancer, especially for complex 21, compared to standard drug doxorubicin. The molecular docking of complexes 20 and 21 has been also studied as Aurora kinase inhibitors.

Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

“…Furthermore, the pyrazolo [1,5-a]pyrimidine moiety is found in some marketed drugs with different biological activities such as: Zaleplon, which is a sedative-hypnotic used to treat insomnia; Ocinaplon, which is an anxiolytic drug; and Dinaciclib (SCH-727965), a cyclin-dependent kinases (CDKs) inhibitor that it is being evaluated in clinical trials for various cancer indications [12,13] (Figure 1). Based on the above facts and in continuation of our target [14][15][16][17][18][19][20][21][22][23][24][25], the purpose of this paper is to evaluate and study the antimicrobial activity {inhibition zone (IZ), the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC) and the minimum fungicidal concentration (MFC)}, the immunomodulatory activity, the physicochemical, pharmacokinetic, and drug-likeness properties, the structure-activity relationship and the molecular docking of pyrazolo [1,5-a] Based on the above facts and in continuation of our target [14][15][16][17][18][19][20][21][22][23][24][25], the purpose of this paper is to evaluate and study the antimicrobial activity {inhibition zone (IZ), the minimum inhibitory concentration (MIC), the minimum bactericidal concentration (MBC) and the minimum fungicidal concentration (MFC)}, the immunomodulatory activity, the physicochemical, pharmacokinetic, and drug-likeness properties, the structure-activity relationship and the molecular docking of pyrazolo [1,5-a]…”

Mixed isatin with 3-(2-(aryl)hydrazono)acetylacetone Mn(II), Co(II) and Ni(II) complexes: antibacterial evaluation and molecular properties prediction

“…In view of these facts and in continuation of our target [13][14][15][16][17][18][19][20][21][22][23][24][25], the metal complexes {Ni(II), Co(II) and Mn(II)} of 3-(2-(aryl)hydrazono)acetylacetone with isatin have been synthesized to evaluate their antibacterial activity against four pathogenic microorganisms {two Gram-positive (Bacillus subtilis and Staphylococcus aureus) and two Gram negative (Escherichia coli and Pseudomonas aeruginosa)}. Also, the study has been extended to calculate the physicochemical properties and drug-likeness (Lipinski's rule) of the mixed ligand metal complexes ( Figure 2).…”

Copper-based glass-ceramic as an efficient catalyst in the synthesis of pyrazolo[1,5-a] pyrimidineunder solvent-free condition with docking validation as Covid-19 main protease (Mpro) inhibitor

“…From the above facts and in continuation of our targets [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33], the presented work aims to introduce a new efficient copper-based oxide glass-ceramic as a catalyst in the synthesis of pyrazolo [1,5-a]pyrimidines 5a-f under solvent-free condition. The work extended to study with docking validation as COVID-19 main protease (M pro ) inhibitor.…”