Re-engineering nalidixic acid's chemical scaffold: A step towards the development of novel anti-tubercular and anti-bacterial leads for resistant pathogens.
Occurrence of antibacterial and antimycobacterial resistance stimulated a thrust to discover new drugs for infectious diseases. Herein we report the work on re-engineering nalidixic acid's chemical scaffold for newer leads. Stepwise clubbing of quinoxaline, 1,2,4-triazole/1,3,4-oxadiazole with nalidixic acid yielded better compounds. Compounds were screened against ciprofloxacin resistant bacteria and Mycobacterium tuberculosis H37Rv species. Results were obtained as minimum inhibitory concentration, it was evident that molecule with quinoxaline linked azide as side chain served as antitubercular lead (<6.25 μg/ml) whilst molecule with oxadiazole or triazole linked quinoxaline side chain served as anti-bacterial lead. Few compounds were significantly active against Escherichia coli and Proteus vulgaris with MIC less than 0.06 μg/ml and relatively potent than ciprofloxacin. No true compound was potentially active against Salmonella species as compared to amoxicillin.
College of Pharmacy, Gulf Medical University, Ajman, United Arab Emirates. Electronic address: rammpharm@rediffmail.com.
Ramalingam
R
Peraman
College of Pharmaceutical Sciences, Andhra University, India.
Raghu Veer
RV
Varma
Medicinal Chemistry Laboratory, Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Anantapur, AP, India.
Y Padmanabha
YP
Reddy
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D009268:Nalidixic Acid / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011514:Proteus vulgaris / Q000187:drug effects*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D009268:Nalidixic Acid; D002939:Ciprofloxacin
Acidhydrazide; Antitubercular; Nalidixic acid; Quinoxaline; Scaffold; Thiosemicarbazide