Synthesis of novel thymol derivatives against MRSA and ESBL producing pathogenic bacteria

Abstract

Twelve substituted aryl-azo-thymol derivatives (4a to 4 l) were synthesized and characterized by several spectral techniques such as, FTIR, UV-vis, proton NMR, Mass spectrometry and elemental analysis. Antimicrobial activities were evaluated by agar-well diffusion method against isolated MRSA, ESBL-producing pathogenic bacteria and antifungal resistant fungi, in vitro. In addition, drug likeness properties of derivatives were assessed through bioinformatic tools such as, PASS prediction, molecular docking and Lipinski rules of five, along with determination of toxic nature and LD₅₀ values. Among 12 derivatives, 4a, 4b, 4c, 4 g, 4i, 4j and 4 k had significant antibacterial and antifungal activities with minimum inhibitory concentration values, 40 to 80 μg/ml. Moreover, the docking scores of derivatives were −8.27 to −11.44 kcal/mol, against 4 bacterial targets and −9.45 to −12.49 kcal/mol against 2 fungal targets. Thus, from in vitro and in silico studies, thymol derivatives had control of MRSA, ESBL-producing bacteria and antifungal resistant fungi.

Keywords:

• Thymol derivative
• antibacterial activities
• antifungal activity
• molecular docking

Acknowledgments

We are grateful to Deans, SPS and IMS and Sum Hospital, Siksha ‘O’ Anusandhan (Deemed to be University), for facilities and encouragements. NMR Spectroscopy was done at NISER, Bhubaneswar, Odisha and the HPLC study at Raghu College of Pharmacy, Visakhapatnam, India.