Attaching azoles to Hantzsch 1,4-dihydropyridines: Synthesis, theoretical investigation of nonlinear optical properties, antimicrobial evaluation and molecular docking studies

GÜNDÜZ M. G., DENGİZ Ç., KOÇAK ASLAN E., Skaro Bogojevic S., Nikodinovic-Runic J.

JOURNAL OF MOLECULAR STRUCTURE, vol.1247, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 1247
  • Publication Date: 2022
  • Doi Number: 10.1016/j.molstruc.2021.131316
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Keywords: Hantzsch reaction, Antifungal, Molecular hybridization, Charge-transfer, Nonlinear optics, Donor-acceptor, AROMATIC NUCLEOPHILIC-SUBSTITUTION, DFT, PERFORMANCE, AMINATION, DESIGN, SERIES, STATE, RING
  • Hacettepe University Affiliated: Yes


In the present study, we designed three novel compounds via the combination of two precious nitrogencontaining scaffolds; 1,4-dihydropyridine (DHP) and azole, in the same molecule. To synthesize the title compounds, initially, azolyl benzaldehydes were obtained through the nucleophilic aromatic substitution reaction of 4-fluorobenzaldehyde with pyrazole, imidazole or 1,2,4-triazole. Subsequently, an unsymmetrical Hantzsch reaction was applied to achieve DHP scaffold, thus the target molecules. After structural characterization, the effects of various azole rings on optical and non-linear optical (NLO) properties were investigated by computational methods. Band gaps, chemical hardness/softness, dipole moments, average polarizability, first hyperpolarizability values were computed for the target compounds at the CAM-B3LYP/6-31++G(d,p) level of theory. The comparable results confirmed the potential of DHP-azole hybrids to be utilized in NLO devices. The title molecules were further tested for their antibacterial and antifungal activities following the evaluation of their drug likeness properties. The compounds containing imidazole or triazole rings represented better antifungal properties than antibacterial activities. Molecular docking studies were performed in the catalytic site of lanosterol 14 alpha-demethylase, CYP51, from Candida albicans to explain the obtained biological results and suggest molecular modifications to endow this class of molecules with improved antifungal effects. (C) 2021 Elsevier B.V. All rights reserved.