Design, Spectroscopic Studies, DFT Calculations and Evaluation of Biological Activity of Novel 1,3-Benzoxazines Encompassing Isoniazid

Abstract

It was planned to utilize isoniazid 1 and substituted salicylaldehydes 2a–f to synthesize some N'-[(E)-(substituted-2-hydroxyphenyl)methylidene]pyridine-4-carbohydrazides 3a–g. Compounds 3a–g on reduction with sodium borohydride in dry methanol with stirring gave N'-[(substituted-2-hydroxyphenyl) methyl] pyridine-4-carbohydrazides 4a–g in good yield. The compounds 4a–g underwent an internal Mannich reaction with formaldehyde (37%) in ethanol for 4–5 h under reflux conditions to give the desired N-(substituted-2H-1,3-benzoxazin-3(4H)-yl)pyridine-4-carboxamides 5a–g. Structures of all the newly synthesized compounds were confirmed by spectral data. All the compounds have been screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Salmonella typhi, antifungal activity against Candida albicans, Cladosporium oxysporum, Aspergillus flavus, and Aspergillus niger and anti-TB activity against M. tuberculosis. The compound 5a indicated significant inhibition against E. coli and A. flavus (MIC-6.25 µg/mL), which was found to be better than the reference drug Gentamycin and Fluconazole respectively. Further, the compound 5d showed more potent anti-TB activity (MIC-1.56 µg/mL) than the reference drug Ciprofloxacin. The DNA cleavage activity for selected compounds was also carried out by the AGE method. To understand the electronic properties of compounds 4a and 5a, DFT calculations at the DFT/B3LYP level using 6-31 G++ (d, p) have been performed to reproduce the geometry and structural features. The non-linear optical property of the compounds 4a and 5a was calculated using first-order hyperpolarisability calculation. The calculated HOMO-LUMO analysis explains the charge transfer interaction between the molecules.

Keywords:

• Isoniazid
• 1
• 3-benzoxazin
• DFT
• anti-microbial
• anti-TB
• DNA cleavage

Acknowledgment

The authors are thankful to the Directors, CDRI, Lucknow and IISc, Bangalore for spectral data. The authors are grateful to The Principal, Vijaya College, R.V. Road, Basavanagudi, Bangalore – 560 004 for providing laboratory facilities. Authors are also thankful to The Director, Skanda Life Sciences Pvt. Ltd., Sunkadakatte, Bengaluru-560 091 for biological studies.

Disclosure statement

The authors report no conflict of interest.