Crystallographic study, biological evaluation and DFT/POM/Docking analyses of pyrazole linked amide conjugates: Identification of antimicrobial and antitumor pharmacophore sites

ABSTRACT Microbes and oxidative stress are among the main causes of many serious diseases. To overcome this scourge, the development and discovery of new antimicrobial and antioxidant agents remain an important lever in the field of medicinal chemistry. Pyrazoles are considered as versatile pharmacophores in the construction of new molecules with excellent activities. In this context, new pyrazole derivatives bearing amide moieties have been synthesized and screened for their antimicrobial and antioxidant activities. The elucidation of the molecular structure of the target compounds was established using the usual spectroscopic techniques (IR, NMR and HRMS), and confirmed by single crystal X-ray diffraction. The crystal structure of the two compounds has been determined. Both crystals belong to the monoclinic system but with different space groups P21/c and P21/n. The crystal cohesion of the two compounds is ensured through hydrogen bonds C–H...O and C–H...π interactions. Two intramolecular hydrogen bonds contribute to the stability of the molecule conformations. The in vitro antimicrobial activity of compounds was tested against S. aureus, E. coli, P. aeruginosa, K. pneumonia, C. albicans and S. cerevisiae strains, and compared with standard antimicrobial drugs with the goal of exploring their potential antimicrobial activity. The obtained bioactivity results were further validated by in silico DFT/Docking studies and POM analysis. In addition, the synthesized compounds were evaluated for their antioxidant activity using the DPPH free radical scavenging test. The results indicated that compounds 5c, 5d, 5e and 5h have a good antioxidant activity comparable with that of standard drugs. Density functional calculations (DFT) were used to analyze the electronic and geometrical characteristics of the target compounds. The identification of pharmacophore sites of tested compounds, based on the Molecular Docking process along with the POM theory, provides important information to be taken into consideration for further research, whereby the objective is to design new more efficient and selective pyrazolic systems, which are likely to materialize as antimicrobial, antioxidant, and antitumor candidates.