Biscoumarin Derivatives as Potent anti-Microbials: Graphene Oxide Catalyzed Eco-Benign Synthesis, Biological Evaluation and Docking Studies

Abstract

A heterogeneous, inexpensive and eco-friendly graphene oxide (GO) catalyst empowered the formation of bioactive biscoumarin derivatives involving domino Knoevenagel–Michael condensation using 4-hydroxycoumarin and aromatic aldehydes in H₂O: EtOH solvent system. The prepared GO was well characterized by Fourier transform infrared (FT-IR), X-ray diffraction spectroscopy (XRD), field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and thermogravimetric analysis (TGA). In this efficient, green, and sustainable one-pot synthesis, the target products were obtained in excellent yields (76–97%) in short reaction time (10–20 min.) and the catalyst can be easily recoverable and reusable for five consecutive cycles. Moreover, the use of economical and easily available substrate, low catalyst loading, shorter reaction time, gram scale applicability and high atom economy are the additional advantages of this greener approach. The inhibitory activity of the synthesized compounds was tested against two species of Gram-negative bacteria (E.Coli MTCC 46 and P. aeruginosa MTCC 2488), two species of Gram-positive bacteria (S. aureus MTCC 6980 and B. megaterium MTCC) and fungus (A. niger MTCC 1344) using the broth microdilution method. The electron withdrawing substituents like -CN, –F, and –Cl exhibited excellent activity against gram negative bacteria as compared to gram positive bacteria. Additionally, in silico studies were carried out on the selected DNA gyrase (1KZN) and human lanosterol 14 alpha-demethylase CYP51 (3LD6) to study the docking interactions of the synthesized compounds. It was observed that out of all the docked compounds, 4e (−23.966 kcal/mol) and 4i (−24.976 kcal/mol) showed highest docking score against 1KZN and 3LD6 protein, respectively.

Graphical Abstract

Keywords:

• Graphene oxide
• green chemistry
• biscoumarins
• antimicrobial activity
• molecular docking

Disclosure statement

The authors confirmed that this article has no conflict of interest.

Acknowledgement

The authors are grateful to Department of Chemistry, M.L.S.U. Udaipur (Raj.), India, for providing necessary laboratory and library facilities and Sophisticated Analytical Instrumentation Facility (SAIF), Chandigarh for spectral analysis. The authors acknowledge Department of Physics, M.L.S.U. Udaipur (Raj.), India for XRD and AFM Measurements.

Additional information

Funding

N. Sahiba and P. Teli are also thankful to CSIR [file no. 09/172(0088)/2018-EMR-I] and [file no. 09/172(0099)/2019-EMR-I] for JRF respectively. A. Sethiya is thankful to UGC-MANF [MANF-2018-19-RAJ-91971] for providing Junior Research Fellowship to carry out this work.