Molecular docking, synthesis, and antimycobacterial activities of pyrrolyl hydrazones and their copper complexes

Abstract:

A novel series of pyrrole derivatives were designed and synthesized with an aim to overcome the growing antitubercular resistance and develop more potent antimicrobial agents. In this pursuit, a novel series of 4-(1H-pyrrol-1-yl)benzoic acid hydrazide Schiff bases were synthesized and reacted with copper acetate to form the respective copper complexes. The reaction of ethyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)benzoate/ethyl-4-(1H-pyrrol-1-yl)benzoate with hydrazine hydrate produced ethyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)benzohydrazide/ethyl 4-(1H-pyrrol-1-yl)benzohydrazide. The reaction of these hydrazides with different aldehydes yielded N′-(arylidene)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzohydrazides/N′-(arylidene)-4-(1H-pyrrol-1-yl)benzohydrazides. Furthermore, these Schiff bases were reacted with copper acetate to produce respective copper complexes. All the synthesized compounds were screened for antitubercular activity using microplate alamar blue assay method that showed reasonably good minimum inhibitory concentration (MIC) values ranging from 3.12 to 50 μg/mL compared to the standard drugs like pyrazinamide (MIC =3.125 μg/mL) and streptomycin (MIC =6.25 μg/mL). The selected compounds were evaluated for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, and Escherichia coli using the broth microdilution assay method. It was found that these compounds exhibited good antibacterial activities in the MIC range of 3.125 to >100 μg/mL when compared against standard drugs like ciprofloxacin and norfloxacin.

Keywords::

• synthesis
• Surflex-Dock
• copper complexes
• antimicrobial activities

Acknowledgments

The authors gratefully acknowledge the financial support from the Council of Scientific and Industrial Research, New Delhi, India (Letter Number 02(0139)/13/EMR-II dated 12/04/2013) and also acknowledge the partial financial support from the Vision Group on Science and Technology, Department of Information Technology, Biotechnology and Science and Technology, Bangalore (File VGST/P-3/SMYSR/GRD-277/2013-14/, dated January 28, 2014). We thank Mr HV Dambal, President, SET’s College of Pharmacy, Dharwad, India, for providing facilities. We also thank Dr KG Bhat, Maratha Mandal’s Dental College, Hospital and Research Centre, Belgaum, India, for antitubercular and antibacterial tests. The Director of SAIF Punjab University, Chandigarh, Punjab, India, and the Director of Indian Institute of Technology, Kanpur, India, have provided NMR and mass spectral data. The authors are grateful to Mr Ravi N Nadigir for his technical assistance. One of the authors (Sheshagiri R Dixit) thanks the authorities of Rajiv Gandhi University of Health Sciences, Bangalore, India.

Disclosure

The authors report no conflicts of interest in this work.