N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity

Niranjan Thota, Parameshwar Makam, Kamal K. Rajbongshi, Savania Nagiah, Naeem Sheik Abdul, Anil A. Chuturgoon, Amit Kaushik, Gyanu Lamichhane, Anou M. Somboro, Hendrik G. Kruger, Thavendran Govender, Tricia Naicker, Per I. Arvidsson

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 μg/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 μg/mL; compound 15 IC50 = 65 μg/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

Original languageEnglish (US)
Pages (from-to)1457-1461
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume10
Issue number10
DOIs
StatePublished - Oct 10 2019

Keywords

  • Mycobacterium abscessus
  • Mycobacterium tuberculosis
  • Sulfonimidamide
  • Trifluoromethylthio
  • cytotoxicity
  • drug discovery
  • medicinal chemistry

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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