Design, Synthesis, and Biological Evaluation of Novel Fused Spiro-4 H-Pyran Derivatives as Bacterial Biofilm Disruptor

Saigal; Mohammad Irfan; Parvez Khan; Mohammad Abid; Md Musawwer Khan

doi:10.1021/acsomega.9b01571

Design, Synthesis, and Biological Evaluation of Novel Fused Spiro-4 H-Pyran Derivatives as Bacterial Biofilm Disruptor

ACS Omega. 2019 Sep 30;4(16):16794-16807. doi: 10.1021/acsomega.9b01571. eCollection 2019 Oct 15.

Authors

Saigal¹, Mohammad Irfan², Parvez Khan², Mohammad Abid², Md Musawwer Khan¹

Affiliations

¹ Department of Chemistry, Aligarh Muslim University, Aligarh 202002, Uttar Pradesh, India.
² Department of Biosciences and Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.

Abstract

This study aims to synthesize novel fused spiro-4H-pyran derivatives under green conditions to develop agents having antimicrobial activity. The synthesized compounds were initially screened for in vitro antibacterial activity against two Gram-positive and three Gram-negative bacterial strains, and all the compounds exhibited moderate to potent antibacterial activity. However, compound 4l showed significant inhibition toward all the bacterial strains, particularly against Streptococcus pneumoniae and Escherichia coli with minimum inhibitory concentration values of 125 μg/mL for each. The toxicity studies of selected compounds (4c, 4e, 4l, and 4m) using human red blood cells as well as human embryonic kidney (HEK-293) cells showed nontoxic behavior at desired concentration. Growth kinetic and time-kill curve studies of 4l against S. pneumoniae and E. coli supported its bactericidal nature. Interestingly, compound 4l showed a synergistic effect when used in combination with ciprofloxacin against selected strains. Biofilm formation in the presence of a lead compound, as assessed by XTT assay, showed complete disruption of the bacterial biofilm visualized by scanning electron microscopy. Overall, the findings suggest 4l to be considered as a promising lead for further development as an antibacterial agent.